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Challenges, Opportunities, and Innovation in Local Drug Delivery
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Challenges, Opportunities, and Innovation in Local Drug Delivery

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 95034

Special Issue Editors

Prof. Dr. Bice Conti

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Guest Editor
Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
Interests: tissue engineering; nanomedicine; drug delivery; nanocarriers; electrospinning
Special Issues, Collections and Topics in MDPI journals
Dr. Ida Genta

E-Mail Website1 Website2
Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: drug delivery; polymer nanoparticles; microspheres; biodegradable polymers; thermosensitive hydrogel; 3D bioprinting; tissue regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Drug delivery is well known to be an opportunity for improving the efficacy and safety of challenging active agents such as those with solubility or toxicity constraints. It broadly refers to approaches, formulations, technologies, and systems for delivering an active agent into the body, also targeting a specific organ or tissue. In this area, local drug delivery systems represent a way to circumvent systemic drug delivery improving site-specific targeted therapies and escaping side effects. Local drug delivery systems can be fabricated from biocompatible and biodegradable materials, exploiting innovative technologies such as electrospinning or microfluidics. The following are some examples: i) electrospun grafts and scaffolds for tissue regeneration loaded with anti-infective, anti-inflammatory drugs, or growth factors, that can improve and speed up tissue regeneration while reducing infection risk, ii) hydrogel and thermosensitive hydrogel-based nanoparticulate drug delivery systems, that offer unique opportunities to locally deliver drugs, i.e., to osteoarthritic joints or an injured spinal cord, and iii) chemotherapeutic loaded stimuli-responsive implantable materials for cancer therapy.

This Special Issue welcomes original research and reviews in this field, with a focus on all aspects of design, characterization, evaluation, and development of novel drug delivery systems for local drug delivery improving and innovating local therapies and tissue regeneration.

Prof. Dr. Bice Conti
Prof. Dr. Ida Genta
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • drug delivery
  • nanomedicine
  • biodegradable polymers
  • stimuli-responsive polymers
  • nanoparticles
  • nanofibers
  • electrospinning
  • 3D-printing

Published Papers (24 papers)

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16 pages, 1753 KiB  
Article
Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study
by Mirjana D. Timotijević, Tanja Ilić, Bojan Marković, Danijela Randjelović, Nebojša Cekić, Ines Nikolić, Snežana Savić and Ivana Pantelić
Int. J. Mol. Sci. 2022, 23(11), 6013; https://doi.org/10.3390/ijms23116013 - 27 May 2022
Cited by 1 | Viewed by 1497
Abstract
Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we [...] Read more.
Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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27 pages, 20700 KiB  
Article
Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells
by Adam Markowski, Anna Jaromin, Paweł Migdał, Ewa Olczak, Adrianna Zygmunt, Magdalena Zaremba-Czogalla, Krzysztof Pawlik and Jerzy Gubernator
Int. J. Mol. Sci. 2022, 23(10), 5536; https://doi.org/10.3390/ijms23105536 - 16 May 2022
Cited by 4 | Viewed by 2837
Abstract
Despite many attempts, trials, and treatment procedures, pancreatic ductal adenocarcinoma (PDAC) still ranks among the most deadly and treatment-resistant types of cancer. Hence, there is still an urgent need to develop new molecules, drugs, and therapeutic methods against PDAC. Naturally derived compounds, such [...] Read more.
Despite many attempts, trials, and treatment procedures, pancreatic ductal adenocarcinoma (PDAC) still ranks among the most deadly and treatment-resistant types of cancer. Hence, there is still an urgent need to develop new molecules, drugs, and therapeutic methods against PDAC. Naturally derived compounds, such as pentacyclic terpenoids, have gained attention because of their high cytotoxic activity toward pancreatic cancer cells. Ursolic acid (UA), as an example, possesses a wide anticancer activity spectrum and can potentially be a good candidate for anti-PDAC therapy. However, due to its minimal water solubility, it is necessary to prepare an optimal nano-sized vehicle to overcome the low bioavailability issue. Poly(lactic-co-glycolic acid) (PLGA) polymeric nanocarriers seem to be an essential tool for ursolic acid delivery and can overcome the lack of biological activity observed after being incorporated within liposomes. PLGA modification, with the addition of PEGylated phospholipids forming the lipid shell around the polymeric core, can provide additional beneficial properties to the designed nanocarrier. We prepared UA-loaded hybrid PLGA/lipid nanoparticles using a nanoprecipitation method and subsequently performed an MTT cytotoxicity assay for AsPC-1 and BxPC-3 cells and determined the hemolytic effect on human erythrocytes with transmission electron microscopic (TEM) visualization of the nanoparticles and their cellular uptake. Hybrid UA-loaded lipid nanoparticles were also examined in terms of their stability, coating dynamics, and ursolic acid loading. We established innovative and repeatable preparation procedures for novel hybrid nanoparticles and obtained biologically active nanocarriers for ursolic acid with an IC50 below 20 µM, with an appropriate size for intravenous dosage (around 150 nm), high homogeneity of the sample (below 0.2), satisfactory encapsulation efficiency (up to 70%) and excellent stability. The new type of hybrid UA-PLGA nanoparticles represents a further step in the development of potentially effective PDAC therapies based on novel, biologically active, and promising triterpenoids. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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26 pages, 9696 KiB  
Article
Influence of the Type of Amino Acid on the Permeability and Properties of Ibuprofenates of Isopropyl Amino Acid Esters
by Paula Ossowicz-Rupniewska, Joanna Klebeko, Ewelina Świątek, Karolina Bilska, Anna Nowak, Wiktoria Duchnik, Łukasz Kucharski, Łukasz Struk, Karolina Wenelska, Adam Klimowicz and Ewa Janus
Int. J. Mol. Sci. 2022, 23(8), 4158; https://doi.org/10.3390/ijms23084158 - 09 Apr 2022
Cited by 14 | Viewed by 2007
Abstract
Modifications of (RS)-2-[4-(2-methylpropyl)phenyl] propanoic acid with amino acid isopropyl esters were synthesised using different methods via a common intermediate. The main reaction was the esterification of the carboxyl group of amino acids with isopropanol and chlorination of the amino group of [...] Read more.
Modifications of (RS)-2-[4-(2-methylpropyl)phenyl] propanoic acid with amino acid isopropyl esters were synthesised using different methods via a common intermediate. The main reaction was the esterification of the carboxyl group of amino acids with isopropanol and chlorination of the amino group of the amino acid, followed by an exchange or neutralisation reaction and protonation. All of the proposed methods were very efficient, and the compounds obtained have great potential to be more effective drugs with increased skin permeability compared with ibuprofen. In addition, it was shown how the introduction of a modification in the form of an ion pair affects the properties of the obtained compound. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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18 pages, 3440 KiB  
Article
Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance
by Frederik Bock, Johan Peter Bøtker, Susan Weng Larsen, Xujin Lu and Jesper Østergaard
Int. J. Mol. Sci. 2022, 23(7), 3599; https://doi.org/10.3390/ijms23073599 - 25 Mar 2022
Cited by 2 | Viewed by 1829
Abstract
A UV imaging release-testing setup comprising an agarose gel as a model for tumorous tissue was developed. The setup was optimized with respect to agarose concentration (0.5% (w/v)), injection procedure, and temperature control. A repeatable injection protocol was established [...] Read more.
A UV imaging release-testing setup comprising an agarose gel as a model for tumorous tissue was developed. The setup was optimized with respect to agarose concentration (0.5% (w/v)), injection procedure, and temperature control. A repeatable injection protocol was established allowing injection into cavities with well-defined geometries. The effective resolution of the SDi2 UV imaging system is 30–80 µm. The linear range of the imaging system is less than that of typical spectrophotometers. Consequently, non-linear cAMP calibration curves were applied for quantification at 280 nm. The degree of deviation from Beer’s law was affected by the background absorbance of the gel matrix. MATLAB scripts provided hitherto missing flexibility with respect to definition and utilization of quantification zones, contour lines facilitating visualization, and automated, continuous data analysis. Various release patterns were observed for an aqueous solution and in situ forming Pluronic F127 hydrogel and PLGA implants containing cAMP as a model for STING ligands. The UV imaging and MATLAB data analysis setup constituted a significant technical development in terms of visualizing behavior for injectable formulations intended for intra-tumoral delivery, and, thereby, a step toward establishment of a bio-predictive in vitro release-testing method. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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17 pages, 1646 KiB  
Article
Targeted Delivery of Cisplatin by Gold Nanoparticles: The Influence of Nanocarrier Surface Modification Type on the Efficiency of Drug Binding Examined by CE-ICP-MS/MS
by Anna M. Wróblewska, Aleksandra Milewska, Marcin Drozd and Magdalena Matczuk
Int. J. Mol. Sci. 2022, 23(4), 2324; https://doi.org/10.3390/ijms23042324 - 19 Feb 2022
Cited by 9 | Viewed by 2348
Abstract
Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, [...] Read more.
Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle–cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold–drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface’s processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH3, and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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18 pages, 2938 KiB  
Article
Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
by Jorge Berlanga-Acosta, Maday Fernández-Mayola, Yssel Mendoza-Marí, Ariana García-Ojalvo, Indira Martinez-Jimenez, Nadia Rodriguez-Rodriguez, Raymond J. Playford, Osvaldo Reyes-Acosta, Laura Lopez-Marín and Gerardo Guillén-Nieto
Int. J. Mol. Sci. 2022, 23(3), 1511; https://doi.org/10.3390/ijms23031511 - 28 Jan 2022
Cited by 1 | Viewed by 2258
Abstract
Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may [...] Read more.
Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats’ full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor’s vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these “vascular disease drivers” may pave novel research avenues for atherosclerosis pathobiology. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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15 pages, 4488 KiB  
Article
Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study
by Mariella Rosalia, Priusha Ravipati, Pietro Grisoli, Rossella Dorati, Ida Genta, Enrica Chiesa, Giovanna Bruni and Bice Conti
Int. J. Mol. Sci. 2021, 22(24), 13557; https://doi.org/10.3390/ijms222413557 - 17 Dec 2021
Cited by 5 | Viewed by 2445
Abstract
Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the [...] Read more.
Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/wPLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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18 pages, 2402 KiB  
Article
Human Epidermal Zinc Concentrations after Topical Application of ZnO Nanoparticles in Sunscreens
by Zahra Khabir, Amy M. Holmes, Yi-Jen Lai, Liuen Liang, Anand Deva, Michael A. Polikarpov, Michael S. Roberts and Andrei V. Zvyagin
Int. J. Mol. Sci. 2021, 22(22), 12372; https://doi.org/10.3390/ijms222212372 - 16 Nov 2021
Cited by 6 | Viewed by 3145
Abstract
Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP [...] Read more.
Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (67Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma–mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that 67ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous 67Zn concentrations in the VE of 1.0 ± 0.3 μg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 μg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 μg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous 67Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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19 pages, 4717 KiB  
Article
Sustainable UV-Crosslinkable Acrylic Pressure-Sensitive Adhesives for Medical Application
by Paula Ossowicz-Rupniewska, Paulina Bednarczyk, Małgorzata Nowak, Anna Nowak, Wiktoria Duchnik, Łukasz Kucharski, Joanna Rokicka, Adam Klimowicz and Zbigniew Czech
Int. J. Mol. Sci. 2021, 22(21), 11840; https://doi.org/10.3390/ijms222111840 - 31 Oct 2021
Cited by 19 | Viewed by 2549
Abstract
This study aimed to investigate the potential of photoreactive acrylate patches as systems for transdermal drug delivery, in particular, using more renewable alternatives and more environmentally friendly synthesis routes of transdermal patches. Therefore, the aim of this study was to develop a transdermal [...] Read more.
This study aimed to investigate the potential of photoreactive acrylate patches as systems for transdermal drug delivery, in particular, using more renewable alternatives and more environmentally friendly synthesis routes of transdermal patches. Therefore, the aim of this study was to develop a transdermal patch containing ibuprofen and investigate its performance in vitro through the pigskin. Transparent patches were prepared using four acrylate copolymers with an incorporated photoinitiator. Two types of transdermal patches based on the photocrosslinking acrylic prepolymers with isobornyl methacrylate as biocomponent and monomer increasing Tg (“hard”) were manufactured. The obtained patches were characterized for their adhesive properties and tested for permeability of the active substance. It turns out that patches whose adhesive matrix is photoreactive polyacrylate copolymers have a higher cohesion than patches from commercial adhesives, while the modification of the copolymers with isobornyl methacrylate resulted in an improvement in adhesion and tack. This study demonstrates the feasibility of developing photoreactive acrylic-based transdermal patches that contain biocomponents that can deliver a therapeutically relevant dose of ibuprofen. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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13 pages, 3824 KiB  
Article
A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues
by Guigen Liu, Veronica Valvo, Sebastian W. Ahn, Devon Thompson, Kyle Deans, Jeon Woong Kang, Sharath Bhagavatula, Christine Dominas and Oliver Jonas
Int. J. Mol. Sci. 2021, 22(21), 11752; https://doi.org/10.3390/ijms222111752 - 29 Oct 2021
Cited by 5 | Viewed by 1962
Abstract
Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While [...] Read more.
Advances in the intratumor measurement of drug responses have included a pioneering biomedical microdevice for high throughput drug screening in vivo, which was further advanced by integrating a graded-index lens based two-dimensional fluorescence micro-endoscope to monitor tissue responses in situ across time. While the previous system provided a bulk measurement of both drug delivery and tissue response from a given region of the tumor, it was incapable of visualizing drug distribution and tissue responses in a three-dimensional (3D) way, thus missing the critical relationship between drug concentration and effect. Here we demonstrate a next-generation system that couples multiplexed intratumor drug release with continuous 3D spatial imaging of the tumor microenvironment via the integration of a miniaturized two-photon micro-endoscope. This enables optical sectioning within the live tissue microenvironment to effectively profile the entire tumor region adjacent to the microdevice across time. Using this novel microimaging-microdevice (MI-MD) system, we successfully demonstrated the four-dimensional imaging (3 spatial dimensions plus time) of local drug delivery in tissue phantom and tumors. Future studies include the use of the MI-MD system for monitoring of localized intra-tissue drug release and concurrent measurement of tissue responses in live organisms, with applications to study drug resistance due to nonuniform drug distribution in tumors, or immune cell responses to anti-cancer agents. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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16 pages, 17636 KiB  
Article
Modification of Magnetite Nanoparticles with Triazine-Based Dendrons and Their Application as Drug-Transporting Systems
by Mateusz Pawlaczyk and Grzegorz Schroeder
Int. J. Mol. Sci. 2021, 22(21), 11353; https://doi.org/10.3390/ijms222111353 - 21 Oct 2021
Cited by 1 | Viewed by 1447
Abstract
The following research aims at the synthesis of magnetite nanoparticles functionalized with triazine-based dendrons and the application of the obtained materials as effective sorptive materials dedicated to acidic bioactive compounds. The adopted synthetic approach involved: (1) the synthesis of nanosized Fe3O [...] Read more.
The following research aims at the synthesis of magnetite nanoparticles functionalized with triazine-based dendrons and the application of the obtained materials as effective sorptive materials dedicated to acidic bioactive compounds. The adopted synthetic approach involved: (1) the synthesis of nanosized Fe3O4 particles via classic co-precipitation method, (2) the introduction of amine groups on their surface leading to materials’ precursor, and (3) the final synthesis of branched triazine-based dendrons on the support surface by an iterative reaction between cyanuric chloride (CC) and piperazine (p) or diethylenetriamine (DETA) via nucleophilic substitution. The characterized materials were tested for their adsorptive properties towards folic acid, 18β–glycyrrhetinic acid, and vancomycin, showing high adsorption capacities varying in the ranges of 53.33–401.61, 75.82–223.71, and 68.17–132.45 mg g−1, respectively. The formed material–drug complexes were also characterized for the drug-delivery potential, performed as in vitro release studies at pH 2.0 and 7.4, which mimics the physiological conditions. The release profiles showed that the proposed materials are able to deliver up to 95.2% of the drugs within 48 h, which makes them efficient candidates for further biomedical applications. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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19 pages, 6806 KiB  
Article
Design and Engineering of “Green” Nanoemulsions for Enhanced Topical Delivery of Bakuchiol Achieved in a Sustainable Manner: A Novel Eco-Friendly Approach to Bioretinol
by Agnieszka Lewińska, Marta Domżał-Kędzia, Ewa Maciejczyk, Marcin Łukaszewicz and Urszula Bazylińska
Int. J. Mol. Sci. 2021, 22(18), 10091; https://doi.org/10.3390/ijms221810091 - 18 Sep 2021
Cited by 15 | Viewed by 4545
Abstract
In the present work, we establish novel “environmentally-friendly” oil-in-water nanoemulsions to enhance the transdermal delivery of bakuchiol, the so-called “bioretinol” obtained from powdered Psoralea corylifolia seeds via a sustainable process, i.e., using a supercritical fluid extraction approach with pure carbon dioxide (SC-CO2 [...] Read more.
In the present work, we establish novel “environmentally-friendly” oil-in-water nanoemulsions to enhance the transdermal delivery of bakuchiol, the so-called “bioretinol” obtained from powdered Psoralea corylifolia seeds via a sustainable process, i.e., using a supercritical fluid extraction approach with pure carbon dioxide (SC-CO2). According to Green Chemistry principles, five novel formulations were stabilized by “green” hybrid ionic surfactants such as coco-betaine—surfactin molecules obtained from coconut and fermented rapeseed meal. Preliminary optimization studies involving three dispersion stability tests, i.e., centrifugation, heating, and cooling cycles, indicated the most promising candidates for further physicochemical analysis. Finally, nanoemulsion colloidal characterization provided by scattering (dynamic and electrophoretic light scattering as well as backscattering), microscopic (transmission electron and confocal laser scanning microscopy), and spectroscopic (UV–Vis spectroscopy) methods revealed the most stable nanocarrier for transdermal biological investigation. In vitro, topical experiments provided on human skin cell line HaCaT keratinocytes and normal dermal NHDF fibroblasts indicated high cell viability upon treatment of the tested formulation with a final 0.02–0.2 mg/mL bakuchiol concentration. This excellent biocompatibility was confirmed by ex vivo and in vivo tests on animal and human skin tissue. The improved permeability and antiaging potential of the bakuchiol-encapsulated rich extract were observed, indicating that the obtained ecological nanoemulsions are competitive with commercial retinol formulations. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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15 pages, 54274 KiB  
Article
Evaluation of Loco-Regional Skin Toxicity Induced by an In Situ Forming Depot after a Single Subcutaneous Injection at Different Volumes and Flow Rates in Göttingen Minipigs
by Charlotte Peloso, Anne-Pascale Trichet, Jacques Descotes, Joël Richard, Christophe Roberge and Adolfo Lopez-Noriega
Int. J. Mol. Sci. 2021, 22(17), 9250; https://doi.org/10.3390/ijms22179250 - 26 Aug 2021
Cited by 1 | Viewed by 4917
Abstract
The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO [...] Read more.
The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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21 pages, 3423 KiB  
Article
Synthesis and Characterization of New Biodegradable Injectable Thermosensitive Smart Hydrogels for 5-Fluorouracil Delivery
by Adam Kasiński, Monika Zielińska-Pisklak, Sebastian Kowalczyk, Andrzej Plichta, Anna Zgadzaj, Ewa Oledzka and Marcin Sobczak
Int. J. Mol. Sci. 2021, 22(15), 8330; https://doi.org/10.3390/ijms22158330 - 03 Aug 2021
Cited by 12 | Viewed by 3077
Abstract
In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene [...] Read more.
In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) and zirconium(IV) acetylacetonate (Zr(acac)4), as co-initiator and catalyst, respectively. The structure, molecular weight (Mn) and molecular weight distribution (Đ) of the synthesized materials was studied in detail using nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the optimal synthesis conditions were determined. The structure corresponded well to the theoretical assumptions. The produced hydrogels demonstrated a sharp sol–gel transition at temperature close to physiological value, forming a stable gel with good mechanical properties at 37 °C. The kinetics and mechanism of in vitro 5-FU release were characterized by zero order, first order, Higuchi and Korsmeyer–Peppas mathematical models. The obtained results indicate good release control; the kinetics were generally defined as first order according to the predominant diffusion mechanism; and the total drug release time was approximately 12 h. The copolymers were considered to be biodegradable and non-toxic; the resulting hydrogels appear to be promising as short-term LDDSs, potentially useful in antitumor therapy. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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17 pages, 3484 KiB  
Article
Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis
by Laura Pandolfi, Alessandro Marengo, Kamila Bohne Japiassu, Vanessa Frangipane, Nicolas Tsapis, Valeria Bincoletto, Veronica Codullo, Sara Bozzini, Monica Morosini, Sara Lettieri, Valentina Vertui, Davide Piloni, Silvia Arpicco, Elias Fattal and Federica Meloni
Int. J. Mol. Sci. 2021, 22(14), 7743; https://doi.org/10.3390/ijms22147743 - 20 Jul 2021
Cited by 8 | Viewed by 3341
Abstract
Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD [...] Read more.
Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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Review

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28 pages, 1514 KiB  
Review
Crossing the Blood-Brain Barrier: Advances in Nanoparticle Technology for Drug Delivery in Neuro-Oncology
by Andrew M. Hersh, Safwan Alomari and Betty M. Tyler
Int. J. Mol. Sci. 2022, 23(8), 4153; https://doi.org/10.3390/ijms23084153 - 09 Apr 2022
Cited by 70 | Viewed by 8863
Abstract
The blood-brain barrier (BBB) constitutes a microvascular network responsible for excluding most drugs from the brain. Treatment of brain tumors is limited by the impermeability of the BBB and, consequently, survival outcomes for malignant brain tumors remain poor. Nanoparticles (NPs) represent a potential [...] Read more.
The blood-brain barrier (BBB) constitutes a microvascular network responsible for excluding most drugs from the brain. Treatment of brain tumors is limited by the impermeability of the BBB and, consequently, survival outcomes for malignant brain tumors remain poor. Nanoparticles (NPs) represent a potential solution to improve drug transport to brain tumors, given their small size and capacity to target tumor cells. Here, we review the unique physical and chemical properties of NPs that aid in BBB transport and discuss mechanisms of NP transport across the BBB, including paracellular transport, carrier-mediated transport, and adsorptive- and receptor-mediated transcytosis. The major types of NPs investigated for treatment of brain tumors are detailed, including polymeric NPs, liposomes, solid lipid NPs, dendrimers, metals, quantum dots, and nanogels. In addition to their role in drug delivery, NPs can be used as imaging contrast agents and can be conjugated with imaging probes to assist in visualizing tumors, demarcating lesion boundaries and margins, and monitoring drug delivery and treatment response. Multifunctional NPs can be designed that are capable of targeting tumors for both imaging and therapeutic purposes. Finally, limitations of NPs for brain tumor treatment are discussed. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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28 pages, 3502 KiB  
Review
Versatile Oral Insulin Delivery Nanosystems: From Materials to Nanostructures
by Mengjie Wang, Chunxin Wang, Shuaikai Ren, Junqian Pan, Yan Wang, Yue Shen, Zhanghua Zeng, Haixin Cui and Xiang Zhao
Int. J. Mol. Sci. 2022, 23(6), 3362; https://doi.org/10.3390/ijms23063362 - 20 Mar 2022
Cited by 19 | Viewed by 6494
Abstract
Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection [...] Read more.
Diabetes is a chronic metabolic disease characterized by lack of insulin in the body leading to failure of blood glucose regulation. Diabetes patients usually need frequent insulin injections to maintain normal blood glucose levels, which is a painful administration manner. Long-term drug injection brings great physical and psychological burden to diabetic patients. In order to improve the adaptability of patients to use insulin and reduce the pain caused by injection, the development of oral insulin formulations is currently a hot and difficult topic in the field of medicine and pharmacy. Thus, oral insulin delivery is a promising and convenient administration method to relieve the patients. However, insulin as a peptide drug is prone to be degraded by digestive enzymes. In addition, insulin has strong hydrophilicity and large molecular weight and extremely low oral bioavailability. To solve these problems in clinical practice, the oral insulin delivery nanosystems were designed and constructed by rational combination of various nanomaterials and nanotechnology. Such oral nanosystems have the advantages of strong adaptability, small size, convenient processing, long-lasting pharmaceutical activity, and drug controlled-release, so it can effectively improve the oral bioavailability and efficacy of insulin. This review summarizes the basic principles and recent progress in oral delivery nanosystems for insulin, including physiological absorption barrier of oral insulin and the development of materials to nanostructures for oral insulin delivery nanosystems. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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29 pages, 2454 KiB  
Review
Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities
by Asad Jamal, Tian Yuan, Stefano Galvan, Antonella Castellano, Marco Riva, Riccardo Secoli, Andrea Falini, Lorenzo Bello, Ferdinando Rodriguez y Baena and Daniele Dini
Int. J. Mol. Sci. 2022, 23(6), 3139; https://doi.org/10.3390/ijms23063139 - 15 Mar 2022
Cited by 12 | Viewed by 3795
Abstract
Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as [...] Read more.
Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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33 pages, 2645 KiB  
Review
Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract
by Yuan Zhang, Juhura G. Almazi, Hui Xin Ong, Matt D. Johansen, Scott Ledger, Daniela Traini, Philip M. Hansbro, Anthony D. Kelleher and Chantelle L. Ahlenstiel
Int. J. Mol. Sci. 2022, 23(5), 2408; https://doi.org/10.3390/ijms23052408 - 22 Feb 2022
Cited by 12 | Viewed by 5510
Abstract
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. [...] Read more.
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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23 pages, 1328 KiB  
Review
Transdermal Drug Delivery Systems and Their Use in Obesity Treatment
by Zhiguo Li, Xuexun Fang and Dahai Yu
Int. J. Mol. Sci. 2021, 22(23), 12754; https://doi.org/10.3390/ijms222312754 - 25 Nov 2021
Cited by 13 | Viewed by 5906
Abstract
Transdermal drug delivery (TDD) has recently emerged as an effective alternative to oral and injection administration because of its less invasiveness, low rejection rate, and excellent ease of administration. TDD has made an important contribution to medical practice such as diabetes, hemorrhoids, arthritis, [...] Read more.
Transdermal drug delivery (TDD) has recently emerged as an effective alternative to oral and injection administration because of its less invasiveness, low rejection rate, and excellent ease of administration. TDD has made an important contribution to medical practice such as diabetes, hemorrhoids, arthritis, migraine, and schizophrenia treatment, but has yet to fully achieve its potential in the treatment of obesity. Obesity has reached epidemic proportions globally and posed a significant threat to human health. Various approaches, including oral and injection administration have widely been used in clinical setting for obesity treatment. However, these traditional options remain ineffective and inconvenient, and carry risks of adverse effects. Therefore, alternative and advanced drug delivery strategies with higher efficacy and less toxicity such as TDD are urgently required for obesity treatment. This review summarizes current TDD technology, and the main anti-obesity drug delivery system. This review also provides insights into various anti-obesity drugs under study with a focus on the recent developments of TDD system for enhanced anti-obesity drug delivery. Although most of presented studies stay in animal stage, the application of TDD in anti-obesity drugs would have a significant impact on bringing safe and effective therapies to obese patients in the future. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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20 pages, 1687 KiB  
Review
Nanoparticle-Based Drug Delivery Systems for Photodynamic Therapy of Metastatic Melanoma: A Review
by Nkune Williams Nkune and Heidi Abrahamse
Int. J. Mol. Sci. 2021, 22(22), 12549; https://doi.org/10.3390/ijms222212549 - 21 Nov 2021
Cited by 14 | Viewed by 3036
Abstract
Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that [...] Read more.
Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that requires a photosensitizer (PS), specific wavelength of light, and molecular oxygen. Several studies using conventional PSs have highlighted the need for improved PSs for PDT applications to achieve desired therapeutic outcomes. The incorporation of nanoparticles (NPs) and targeting moieties in PDT have appeared as a promising strategy to circumvent various drawbacks associated with non-specific toxicity, poor water solubility, and low bioavailability of the PSs at targeted tissues. Currently, most studies investigating new developments rely on two-dimensional (2-D) monocultures, which fail to accurately mimic tissue complexity. Therefore, three-dimensional (3-D) cell cultures are ideal models to resemble tumor tissue in terms of architectural and functional properties. This review examines various PS drugs, as well as passive and active targeted PS nanoparticle-mediated platforms for PDT treatment of MM on 2-D and 3-D models. The overall findings of this review concluded that very few PDT studies have been conducted within 3-D models using active PS nanoparticle-mediated platforms, and so require further investigation. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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30 pages, 18278 KiB  
Review
Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye
by Alexander Vaneev, Victoria Tikhomirova, Natalia Chesnokova, Ekaterina Popova, Olga Beznos, Olga Kost and Natalia Klyachko
Int. J. Mol. Sci. 2021, 22(22), 12368; https://doi.org/10.3390/ijms222212368 - 16 Nov 2021
Cited by 40 | Viewed by 7280
Abstract
Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy [...] Read more.
Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients. However, conventional drug formulations are usually characterized by short retention time in the tear film, insufficient contact with epithelium, fast elimination, and difficulties in overcoming ocular tissue barriers. Not more than 5% of the total drug dose administered in eye drops reaches the interior ocular tissues. To overcome the ocular drug delivery barriers and improve drug bioavailability, various conventional and novel drug delivery systems have been developed. Among these, nanosize carriers are the most attractive. The review is focused on the different drug carriers, such as synthetic and natural polymers, as well as inorganic carriers, with special attention to nanoparticles and nanomicelles. Studies in vitro and in vivo have demonstrated that new formulations could help to improve the bioavailability of the drugs, provide sustained drug release, enhance and prolong their therapeutic action. Promising results were obtained with drug-loaded nanoparticles included in in situ gel. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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39 pages, 2274 KiB  
Review
Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels
by Michał Smoleński, Bożena Karolewicz, Anna M. Gołkowska, Karol P. Nartowski and Katarzyna Małolepsza-Jarmołowska
Int. J. Mol. Sci. 2021, 22(12), 6455; https://doi.org/10.3390/ijms22126455 - 16 Jun 2021
Cited by 15 | Viewed by 5435
Abstract
In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and [...] Read more.
In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and physiological variability resulting in unsatisfactory therapeutic efficacy of lipophilic active substances requires application of multicompartment drug delivery systems. This manuscript provides an up-to-date comprehensive review of the literature on emulsion-based vaginal dosage forms (EVDF) including macroemulsions, microemulsions, nanoemulsions, multiple emulsions and self-emulsifying drug delivery systems. The first part of the paper discusses (i) the influence of anatomical-physiological conditions on therapeutic efficacy of drug forms after local and systemic administration, (ii) characterization of EVDF components and the manufacturing techniques of these dosage forms and (iii) methods used to evaluate the physicochemical and pharmaceutical properties of emulsion-based vaginal dosage forms. The second part of the paper presents (iv) the results of biological and in vivo studies as well as (v) clinical evaluation of EVDF safety and therapeutic efficacy across different indications. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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30 pages, 801 KiB  
Review
Achievements in Thermosensitive Gelling Systems for Rectal Administration
by Maria Bialik, Marzena Kuras, Marcin Sobczak and Ewa Oledzka
Int. J. Mol. Sci. 2021, 22(11), 5500; https://doi.org/10.3390/ijms22115500 - 23 May 2021
Cited by 24 | Viewed by 4669
Abstract
Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of [...] Read more.
Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems. Full article
(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery)
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