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Nanomedicine as a Tool to Improve the Local Delivery of...
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Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 November 2021) | Viewed by 37384

Special Issue Editors

Prof. Dr. Roberta Cavalli

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Guest Editor
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via P. Giuria 9, 10125 Torino, Italy
Interests: nanoparticles; drug delivery systems; cyclodextrins; DNA delivery
Special Issues, Collections and Topics in MDPI journals
Dr. Monica Argenziano

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Guest Editor
Department of Drug Science and Technology, University of Turin, Turin, Italy
Interests: drug delivery; nanocarriers; topical delivery
Special Issues, Collections and Topics in MDPI journals
Dr. Chiara Bastiancich

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Guest Editor
Department of Drug Science and Technology, University of Turin, 10124 Turin, Italy
Interests: glioblastomas; brain drug delivery; nanomedicine; preclinical model; drug repurposing; surgery; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The local delivery of active molecules is an excellent strategy to bypass biological barriers, obtaining targeted efficacy at reduced doses and with limited side effects. Nanocarriers can be used to deliver the active molecules in order to increase their stability, avoid drug resistance mechanisms, or selectively target certain cell populations. Moreover, nanomedicines can have intrinsic properties that allow them to adapt and adhere to the target site, induce sustained or environmental triggered drug release, or enhance their penetration depth into biological tissues.

In this Special Issue, we aim to collect articles regarding this topic in order to demonstrate the potential of this drug delivery strategy in a wide range of applications (from cancer treatment to gene therapy, from intracerebral to intra-articular drug delivery).

Prof. Dr. Roberta Cavalli
Dr. Monica Argenziano
Dr. Chiara Bastiancich
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • nanomedicine
  • drug delivery
  • local delivery
  • active molecules
  • biomaterials
  • sustained release
  • targeted medicine
  • drug absorption
  • permeability
  • biological barriers
  • theranostics
  • local treatment
  • nanocarriers

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Published Papers (9 papers)

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Research

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10 pages, 1789 KiB  
Article
Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery
by Phoebe McCrorie, Jonathan Rowlinson, David J. Scurr, Maria Marlow and Ruman Rahman
Pharmaceutics 2022, 14(3), 571; https://doi.org/10.3390/pharmaceutics14030571 - 5 Mar 2022
Cited by 5 | Viewed by 3207
Abstract
Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetration of label-free drugs, an absence of efficacy typically hampers clinical translational [...] Read more.
Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetration of label-free drugs, an absence of efficacy typically hampers clinical translational potential, rather than encourage re-formulation of drug compounds using nanocarriers to achieve greater tissue penetration. OrbiSIMS, a next-generation analytical instrument for label-free imaging, combines the high resolving power of an OrbiTrapTM mass spectrometer with the relatively high spatial resolution of secondary ion mass spectrometry. Here, we develop an ex vivo pipeline using OrbiSIMS to accurately detect brain penetration of drug compounds. Secondary ion spectra were acquired for a panel of drugs (etoposide, olaparib, gemcitabine, vorinostat and dasatinib) under preclinical consideration for the treatment of isocitrate dehydrogenase-1 wild-type glioblastoma. Each drug demonstrated diagnostic secondary ions (all present molecular ions [M-H]− which could be discriminated from brain analytes when spiked at >20 µg/mg tissue. Olaparib/dasatinib and olaparib/etoposide dual combinations are shown as exemplars for the capability of OrbiSIMS to discriminate distinct drug ions simultaneously. Furthermore, we demonstrate the imaging capability of OrbiSIMS to simultaneously illustrate label-free drug location and brain chemistry. Our work encourages the neuro-oncology community to consider mass spectrometry imaging modalities to complement in vivo efficacy studies, as an analytical tool to assess brain distribution of systemically administered drugs, or localised brain penetration of drugs released from micro- or nano-scale biomaterials. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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14 pages, 3945 KiB  
Article
Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy
by Ben Newland, Johannes Starke, Chiara Bastiancich, Diana P. N. Gonçalves, Laura J. Bray, Wenxin Wang and Carsten Werner
Pharmaceutics 2022, 14(3), 551; https://doi.org/10.3390/pharmaceutics14030551 - 28 Feb 2022
Cited by 5 | Viewed by 4901
Abstract
Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a [...] Read more.
Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood–brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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14 pages, 1424 KiB  
Article
Preparation and Optimization of Garlic Oil/Apple Cider Vinegar Nanoemulsion Loaded with Minoxidil to Treat Alopecia
by Waleed Y. Rizg, Khaled M. Hosny, Samar S. Elgebaly, Abdulmohsin J. Alamoudi, Raed I. Felimban, Hossam H. Tayeb, Majed Alharbi, Haitham A. Bukhary, Walaa A. Abualsunun, Alshaimaa M. Almehmady and Rasha A. Khallaf
Pharmaceutics 2021, 13(12), 2150; https://doi.org/10.3390/pharmaceutics13122150 - 14 Dec 2021
Cited by 18 | Viewed by 7156
Abstract
Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple [...] Read more.
Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple cider vinegar (APCV) and loaded with minoxidil (MX) in order to enhance drug solubilization and permeation through skin. A distance coordinate exchange quadratic mixture design was used to optimize the proposed nanoemulsion. Span 20 and Tween 20 mixtures were used as the surfactant, and Transcutol was used as the co-surfactant. The developed formulations were characterized for their droplet size, minoxidil steady-state flux (MX Jss) and minimum inhibitory concentration (MIC) against Propionibacterium acnes. The optimized MX-GO-APCV nanoemulsion had a droplet size of 110 nm, MX Jss of 3 μg/cm2 h, and MIC of 0.275 μg/mL. The optimized formulation acquired the highest ex vivo skin permeation parameters compared to MX aqueous dispersion, and varying formulations lacked one or more components of the proposed nanoemulsion. GO and APCV in the optimized formulation had a synergistic, enhancing activity on the MX permeation across the skin membrane, and the percent permeated increased from 12.7% to 41.6%. Finally, the MX-GO-APCV nanoemulsion followed the Korsmeyer–Peppas model of diffusion, and the value of the release exponent (n) obtained for the formulations was found to be 1.0124, implying that the MX permeation followed Super case II transport. These results demonstrate that the MX-GO-APCV nanoemulsion formulation could be useful in promoting MX activity in treating alopecia areata. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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33 pages, 4963 KiB  
Article
Lipid Nanocarriers-Loaded Nanocomposite as a Suitable Platform to Release Antibacterial and Antioxidant Agents for Immediate Dental Implant Placement Restorative Treatment
by Giuseppe Angellotti, Alessandro Presentato, Denise Murgia, Giulia Di Prima, Fabio D’Agostino, Amalia Giulia Scarpaci, Maria Cristina D’Oca, Rosa Alduina, Giuseppina Campisi and Viviana De Caro
Pharmaceutics 2021, 13(12), 2072; https://doi.org/10.3390/pharmaceutics13122072 - 3 Dec 2021
Cited by 15 | Viewed by 2849
Abstract
Immediate implant placement is a single-stage restorative approach for missing teeth widely used to overcome the ridge remodeling process occurring after dental extractions. The success of this procedure relies on opportune osseointegration in the surrounding tissues. To support this process, a multifunctional nanocomposite, [...] Read more.
Immediate implant placement is a single-stage restorative approach for missing teeth widely used to overcome the ridge remodeling process occurring after dental extractions. The success of this procedure relies on opportune osseointegration in the surrounding tissues. To support this process, a multifunctional nanocomposite, to be applied in the fresh post-extraction socket, was here designed, prepared, and characterized. This formulation consists of quercetin (QRC)-loaded nanostructured lipid carriers (NLCs) entrapped in a chitosan-based solid matrix containing ciprofloxacin (CPX). QRC-NLCs were prepared by homogenization followed by high-frequency sonication, and thereafter this dispersion was trapped in a chitosan-based CPX-loaded gel, obtaining the nanocomposite powder (BioQ-CPX) by lyophilization. BioQ-CPX displayed desirable properties such as high porosity (94.1 ± 0.5%), drug amounts (2.1% QRC and 3.5% CPX). and low swelling index (100%). Moreover, the mechanism of drug release from BioQ-CPX and their ability to be accumulated in the target tissue were in vitro and ex vivo elucidated, also by applying mathematical models. When trapped into the nanocomposite, QRC stressed under UV light exposure (50 W) was shown to maintain its antioxidant power, and CPX and QRC under natural light were stable over nine months. Finally, both the measured antioxidant power and the antimicrobial and antibiofilm properties on Staphylococcus aureus demonstrated that BioQ-CPX could be a promising platform to support the single-stage dental restorative treatment. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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14 pages, 5719 KiB  
Article
The Impact of Bilayer Rigidity on the Release from Magnetoliposomes Vesicles Controlled by PEMFs
by Jordan Trilli, Laura Caramazza, Patrizia Paolicelli, Maria Antonietta Casadei, Micaela Liberti, Francesca Apollonio and Stefania Petralito
Pharmaceutics 2021, 13(10), 1712; https://doi.org/10.3390/pharmaceutics13101712 - 16 Oct 2021
Cited by 10 | Viewed by 2931
Abstract
Stimuli-sensitive nanocarriers have recently been developed as a powerful tool in biomedical applications such as drug delivery, detection, and gene transfer techniques. Among the external triggers investigated, low intensity magnetic fields represent a non-invasive way to remotely control the release of compounds from [...] Read more.
Stimuli-sensitive nanocarriers have recently been developed as a powerful tool in biomedical applications such as drug delivery, detection, and gene transfer techniques. Among the external triggers investigated, low intensity magnetic fields represent a non-invasive way to remotely control the release of compounds from a magneto-sensitive carrier. Magnetoliposomes (MLs), i.e., liposomes entrapping magnetic nanoparticles (MNPs), are studied due to their capacity to transport hydrophobic and hydrophilic agents, their easy production, and due to the ability of MNPs to respond to a magnetic actuation determining the triggered release of the encapsulated compounds. Here we investigated the design and optimization of the MLs to obtain an efficient on-demand release of the transported compounds, due to the magneto-mechanical actuation induced by applying low-intensity pulsed electromagnetic fields (PEMFs). In particular we studied the effect of the bilayer packing on the ability of MLs, with oleic acid-coated MNPs encapsulated in the bilayer, to respond to PEMFs application. Three kinds of MLs are produced with an increasing rigidity of the bilayer, defined as Liquid Disorder, Liquid Order, and Gel MLs and the delivery of a hydrophilic dye (as a model drug) is investigated. Results demonstrate the efficacy of the magnetic trigger on high-ordered bilayers, which are unable to dampen the perturbation produced by MNPs motion. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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16 pages, 2340 KiB  
Article
Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure
by Hesham A. Saafan, Kamilia M. Ibrahim, Yasmeena Thabet, Sara M. Elbeltagy, Rana A. Eissa, Ashraf H. Ghaleb, Fathy Ibrahim, Mahmoud Elsabahy and Noura G. Eissa
Pharmaceutics 2021, 13(10), 1677; https://doi.org/10.3390/pharmaceutics13101677 - 14 Oct 2021
Cited by 15 | Viewed by 2742
Abstract
Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential [...] Read more.
Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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20 pages, 6611 KiB  
Article
Multifunctional Nanofibrous Dressing with Antimicrobial and Anti-Inflammatory Properties Prepared by Needle-Free Electrospinning
by Laura Victoria Schulte-Werning, Anjanah Murugaiah, Bhupender Singh, Mona Johannessen, Rolf Einar Engstad, Nataša Škalko-Basnet and Ann Mari Holsæter
Pharmaceutics 2021, 13(9), 1527; https://doi.org/10.3390/pharmaceutics13091527 - 21 Sep 2021
Cited by 18 | Viewed by 4103
Abstract
An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and [...] Read more.
An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and CHI are active nanofiber-forming biopolymers isolated from the cell walls of Saccharomyces cerevisiae and from shrimp shells, respectively. To evaluate the effect of each active ingredient on the nanofibers’ morphological features and bioactivity, nanofibers with both βG and CHI, only βG, only CHI and only copolymers, polyethylene oxide (PEO) and hydroxypropylmethylcellulose (HPMC) were fabricated. All four nanofiber formulations were also prepared with 1% CAM. The needle-free NanospiderTM technique allowed for the successful production of defect-free nanofibers containing all three active ingredients. The CAM-containing nanofibers had a burst CAM-release and a high absorption capacity. Nanofibers with all active ingredients (βG, CHI and CAM) showed a concentration-dependent anti-inflammatory activity, while maintaining the antimicrobial activity of CAM. The promising anti-inflammatory properties, together with the high absorption capacity and antimicrobial effect, make these multifunctional nanofibers promising as dressings in local treatment of infected and exuding wounds, such as burn wounds. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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17 pages, 3721 KiB  
Article
Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles
by Misa Minami, Hiroko Otake, Yosuke Nakazawa, Norio Okamoto, Naoki Yamamoto, Hiroshi Sasaki and Noriaki Nagai
Pharmaceutics 2021, 13(9), 1425; https://doi.org/10.3390/pharmaceutics13091425 - 8 Sep 2021
Cited by 8 | Viewed by 2840
Abstract
We previously designed ophthalmic formulations (nTRA) containing tranilast nanoparticles (Tra-NPs) with high uptake into ocular tissues. In this study, we used in situ gel (ISG) bases comprising combinations of pluronic F127 (F127) and methylcellulose (MC/F127), pluronic F68 (F68/F127), and Carbopol (Car/F127), and we [...] Read more.
We previously designed ophthalmic formulations (nTRA) containing tranilast nanoparticles (Tra-NPs) with high uptake into ocular tissues. In this study, we used in situ gel (ISG) bases comprising combinations of pluronic F127 (F127) and methylcellulose (MC/F127), pluronic F68 (F68/F127), and Carbopol (Car/F127), and we developed in situ gels incorporating Tra-NPs (Tra-NP-incorporated ISNGs) such as nTRA-F127, nTRA-MC/F127, nTRA-F68/F127, and nTRA-Car/F127. Moreover, we demonstrated the therapeutic effect on conjunctival inflammation using lipopolysaccharide-induced rats. Each Tra-NP-incorporated ISNG was prepared by the bead mill method, the particle size was 40–190 nm, and the tranilast release and diffusion from formulation were nTRA > nTRA-F127 > nTRA-F68/F127 > nTRA-Car/F127 > nTRA-MC/F127. In the Tra-NP-incorporated ISNGs, the tranilast residence time in the lacrimal fluid, cornea, and conjunctiva was prolonged, although the Cmax was attenuated in comparison with nTRA. On the other hand, no significant difference in conjunctival inflammation between non- and nTRA-F127-instilled rats was found; however, the nTRA-F68/F127, nTRA-Car/F127, and nTRA-MC/F127 (combination-ISG) attenuated the vessel leakage, nitric oxide, and tumor necrosis factor-α expression. In particular, nTRA-F68/F127 was significant in preventing the conjunctival inflammation. In conclusion, we found that the combination-ISG base prolonged the residence time of Tra-NPs; however, Tra-NP release from the formulation was attenuated, and the Tmax was delayed longer than that in nTRA. The balance of drug residence and diffusion in lacrimal fluid may be important in providing high ocular bioavailability in formulations containing solid nanoparticles. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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Review

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27 pages, 2168 KiB  
Review
Nanocarriers as a Tool for the Treatment of Colorectal Cancer
by Ana Luiza C. de S. L. Oliveira, Timo Schomann, Lioe-Fee de Geus-Oei, Ellen Kapiteijn, Luis J. Cruz and Raimundo Fernandes de Araújo Junior
Pharmaceutics 2021, 13(8), 1321; https://doi.org/10.3390/pharmaceutics13081321 - 23 Aug 2021
Cited by 15 | Viewed by 5261
Abstract
Nanotechnology is a promising tool for the treatment of cancer. In the past decades, major steps have been made to bring nanotechnology into the clinic in the form of nanoparticle-based drug delivery systems. The great hope of drug delivery systems is to reduce [...] Read more.
Nanotechnology is a promising tool for the treatment of cancer. In the past decades, major steps have been made to bring nanotechnology into the clinic in the form of nanoparticle-based drug delivery systems. The great hope of drug delivery systems is to reduce the side effects of chemotherapeutics while simultaneously increasing the efficiency of the therapy. An increased treatment efficiency would greatly benefit the quality of life as well as the life expectancy of cancer patients. However, besides its many advantages, nanomedicines have to face several challenges and hurdles before they can be used for the effective treatment of tumors. Here, we give an overview of the hallmarks of cancer, especially colorectal cancer, and discuss biological barriers as well as how drug delivery systems can be utilized for the effective treatment of tumors and metastases. Full article
(This article belongs to the Special Issue Nanomedicine as a Tool to Improve the Local Delivery of Active Molecules)
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