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Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 12820

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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

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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,

It is well known that drug delivery represents an opportunity to improve 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, as well as targeting a specific organ or tissue. In this area, local drug delivery systems represent a way in which 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 or anti-inflammatory drugs, or growth factors, which can improve and accelerate tissue regeneration, while reducing infection risk; ii) hydrogel and thermosensitive hydrogel-based nanoparticulate drug delivery systems, which 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 particular focus on all aspects of the design, characterization, evaluation, and development of novel drug delivery systems for improving local drug delivery and innovating local therapies and tissue regeneration.

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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 (5 papers)

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Research

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19 pages, 3554 KiB

Open AccessArticle

Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148

by Muhanad Ali, Miriam E. van Gent, Amy M. de Waal, Bjorn R. van Doodewaerd, Erik Bos, Roman I. Koning, Robert A. Cordfunke, Jan Wouter Drijfhout and Peter H. Nibbering

Int. J. Mol. Sci. 2023, 24(3), 2867; https://doi.org/10.3390/ijms24032867 - 02 Feb 2023

Cited by 5 | Viewed by 1999

Abstract

Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant antimicrobial activities against antimicrobial resistant (AMR) planktonic bacteria and biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity and antimicrobial activity, as well as its bioavailability at infection sites. We hypothesized that formulation of SAAP-148 in PLGA nanoparticles (SAAP-148 NPs) improves the selectivity index due to the sustained local release of the peptide. The aim of this study was to investigate the physical and functional characteristics of SAAP-148 NPs and to compare the selectivity index of the formulated peptide with that of the peptide in solution. SAAP-148 NPs displayed favorable physiochemical properties [size = 94.1 ± 23 nm, polydispersity index (PDI) = 0.08 ± 0.1, surface charge = 1.65 ± 0.1 mV, and encapsulation efficiency (EE) = 86.7 ± 0.3%] and sustained release of peptide for up to 21 days in PBS at 37 °C. The antibacterial and cytotoxicity studies showed that the selectivity index for SAAP-148 NPs was drastically increased, by 10-fold, regarding AMR Staphylococcus aureus and 20-fold regarding AMR Acinetobacter baumannii after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR S. aureus and A. baumannii gradually increased overtime, suggesting a dose–effect relationship based on the peptide’s in vitro release profile. Using 3D human skin equivalents (HSEs), dual drug SAAP-148 NPs and the novel antibiotic halicin NPs provided a stronger antibacterial response against planktonic and cell-associated bacteria than SAAP-148 NPs but not halicin NPs after 24 h. Confocal laser scanning microscopy revealed the presence of SAAP-148 NPs on the top layers of the skin models in close proximity to AMR S. aureus at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections. Full article

(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0)

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13 pages, 6966 KiB

Open AccessArticle

AAV13 Enables Precise Targeting of Local Neural Populations

by Zengpeng Han, Nengsong Luo, Yang Wu, Jiaxin Kou, Wenyu Ma, Xin Yang, Yuxiang Cai, Lin Ma, Lu Han, Xiujie Wang, Hualing Qin, Qing Shi, Jie Wang, Chaohui Ye, Kunzhang Lin and Fuqiang Xu

Int. J. Mol. Sci. 2022, 23(21), 12806; https://doi.org/10.3390/ijms232112806 - 24 Oct 2022

Cited by 3 | Viewed by 2445

Abstract

As powerful tools for local gene delivery, adeno-associated viruses (AAVs) are widely used for neural circuit studies and therapeutical purposes. However, most of them have the characteristics of large diffusion range and retrograde labeling, which may result in off-target transduction during in vivo application. Here, in order to achieve precise gene delivery, we screened AAV serotypes that have not been commonly used as gene vectors and found that AAV13 can precisely transduce local neurons in the brain, with a smaller diffusion range than AAV2 and rigorous anterograde labeling. Then, AAV13-based single-viral and dual-viral strategies for sparse labeling of local neurons in the brains of C57BL/6 or Cre transgenic mice were developed. Additionally, through the neurobehavioral test in the ventral tegmental area, we demonstrated that AAV13 was validated for functional monitoring by means of carrying Cre recombinase to drive the expression of Cre-dependent calcium-sensitive indicator. In summary, our study provides AAV13-based toolkits for precise local gene delivery, which can be used for in situ small nuclei targeting, sparse labeling and functional monitoring. Full article

(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0)

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16 pages, 3306 KiB

Open AccessArticle

Dexamethasone-Loaded Hydrogels Improve Motor and Cognitive Functions in a Rat Mild Traumatic Brain Injury Model

by Christian Macks, Daun Jeong, Sooneon Bae, Ken Webb and Jeoung Soo Lee

Int. J. Mol. Sci. 2022, 23(19), 11153; https://doi.org/10.3390/ijms231911153 - 22 Sep 2022

Cited by 10 | Viewed by 1945

Abstract

Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment. Full article

(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0)

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13 pages, 2955 KiB

Open AccessArticle

A Dioscorea opposita Thunb Polysaccharide-Based Dual-Responsive Hydrogel for Insulin Controlled Release

by Wei Liu, Xiaoge Wang, Danyang Zhou, Xiangze Fan, Jinhua Zhu and Xiuhua Liu

Int. J. Mol. Sci. 2022, 23(16), 9081; https://doi.org/10.3390/ijms23169081 - 13 Aug 2022

Cited by 4 | Viewed by 1765

Abstract

A novel hydrogel (DOP/PEI-PBA) based on the “three-component” reaction of 2-formylphenylboric acid (2-FPBA), the primary amine group of polyethyleneimine (PEI) and the cis-o-dihydroxy groups of Dioscorea opposita Thunb polysaccharide (DOP) was designed in this work. The hydrogel can be easily prepared by simply mixing the three reactants at room temperature. The hydrogel had dual responsiveness to glucose and pH, and can realize the controllable release of insulin. Moreover, the hydrogel combining insulin and DOP can inhibit the reactive oxygen species (ROS) level and malondialdehyde (MDA) content, and promote glucose consumption as well as the level of superoxide dismutase (SOD), in high-glucose-induced injury in HL-7702 cells, which reflects the synergistic effect of insulin and DOP to protect hepatocytes from oxidative stress at the same time. Further in vitro cytotoxicity studies showed that the hydrogel had good biocompatibility and no obvious toxicity to cells. These indicate that the prepared hydrogel (DOP/PEI-PBA) can be expected to be applied in the clinical treatment of insulin deficiency in diabetes. Full article

(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0)

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Review

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34 pages, 6198 KiB

Open AccessReview

Lipid-Based Nanoparticles as a Pivotal Delivery Approach in Triple Negative Breast Cancer (TNBC) Therapy

by Aiswarya Chaudhuri, Dulla Naveen Kumar, Rasheed A. Shaik, Basma G. Eid, Ashraf B. Abdel-Naim, Shadab Md, Aftab Ahmad and Ashish Kumar Agrawal

Int. J. Mol. Sci. 2022, 23(17), 10068; https://doi.org/10.3390/ijms231710068 - 03 Sep 2022

Cited by 26 | Viewed by 3490

Abstract

Triple-negative breast cancer is considered the most aggressive type of breast cancer among women and the lack of expressed receptors has made treatment options substantially limited. Recently, various types of nanoparticles have emerged as a therapeutic option against TNBC, to elevate the therapeutic efficacy of the existing chemotherapeutics. Among the various nanoparticles, lipid-based nanoparticles (LNPs) viz. liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid nanocarriers, and lipid–polymer hybrid nanoparticles are developed for cancer treatment which is well confirmed and documented. LNPs include various therapeutic advantages as compared to conventional therapy and other nanoparticles, including increased loading capacity, enhanced temporal and thermal stability, decreased therapeutic dose and associated toxicity, and limited drug resistance. In addition to these, LNPs overcome physiological barriers which provide increased accumulation of therapeutics at the target site. Extensive efforts by the scientific community could make some of the liposomal formulations the clinical reality; however, the relatively high cost, problems in scaling up the formulations, and delivery in a more targetable fashion are some of the major issues that need to be addressed. In the present review, we have compiled the state of the art about different types of LNPs with the latest advances reported for the treatment of TNBC in recent years, along with their clinical status and toxicity in detail. Full article

(This article belongs to the Special Issue Challenges, Opportunities, and Innovation in Local Drug Delivery 2.0)

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