Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.9
5.4
Journals
Pharmaceutics
Special Issues
Recent Developments in Polymer–Drug Conjugates
share announcement

Recent Developments in Polymer–Drug Conjugates

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (10 November 2021) | Viewed by 15686

Special Issue Editors

Dr. Francesca Greco

E-Mail Website
Guest Editor
Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AP, UK
Interests: drug delivery; polymer–drug conjugates; EPR effect; nanotechnology
Mr. Az Alddien Natfji

E-Mail Website
Co-Guest Editor
Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK
Interests: polymer-drug conjugates; biological barriers; cancer; angiogenesis

Special Issue Information

Dear Colleagues,

2020 will mark 45 years since the publication of Ringsdorf’s seminal paper, in which the concept of covalently linking a drug to a polymeric carrier to improve drug delivery was first proposed. Initial studies focused on the optimization of polymer size and linkers and were  developed for application to cancer. Recent years have seen some very significant changes in the field. Polymer–drug conjugates have been suggested for a much broader pool of therapeutic applications. Furthermore, new discoveries on the enhanced permeability and retention (EPR) effect are strengthening the rational design of these systems. 

For this Special Issue, we welcome original articles on polymer–drug conjugates. Articles that describe new polymers, new applications of polymer–drug conjugates, and new discoveries on the EPR effect are welcome. Within the issue we want to highlight recent innovations in the field; so, the list above is indicative and not exhaustive. 

Dr. Francesca Greco
Mr. Az Alddien Natfji
Guest Editor

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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

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

  • polymer–drug conjugates
  • enhanced permeability and retention (EPR) effect
  • nanotechnologies
  • polymer
  • drug delivery

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

17 pages, 3230 KiB  
Article
Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model
by Tzu-Yang Chen, Ching-Li Tseng, Chih-An Lin, Hua-Yang Lin, Parthiban Venkatesan and Ping-Shan Lai
Pharmaceutics 2021, 13(9), 1366; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091366 - 30 Aug 2021
Cited by 9 | Viewed by 5288
Abstract
Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to [...] Read more.
Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompatibility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis®, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Importantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical application. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E2 (PGE2) in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES. Full article
(This article belongs to the Special Issue Recent Developments in Polymer–Drug Conjugates)
►▼ Show Figures

Figure 1

15 pages, 2349 KiB  
Article
A Novel Polymer Insect Repellent Conjugate for Extended Release and Decreased Skin Permeation of Para-Menthane-3,8-Diol
by Sayyed I. Shah, Vitaliy V. Khutoryanskiy and Adrian C. Williams
Pharmaceutics 2021, 13(3), 403; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030403 - 18 Mar 2021
Cited by 3 | Viewed by 2669
Abstract
Background: We developed a novel polymer insect repellent conjugate for extended release and decreased skin permeation of the volatile insect repellent p-menthane-3,8-diol (PMD). Methods: PMD was conjugated with acryloyl chloride via an ester bond to form acryloyl–PMD, which was subsequently copolymerised with acrylic [...] Read more.
Background: We developed a novel polymer insect repellent conjugate for extended release and decreased skin permeation of the volatile insect repellent p-menthane-3,8-diol (PMD). Methods: PMD was conjugated with acryloyl chloride via an ester bond to form acryloyl–PMD, which was subsequently copolymerised with acrylic acid at varying molar ratios. Copolymer structures were characterised by 1H NMR and FT-IR, analysed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), molecular weights and reactivity ratios determined, and repellent loading assessed. Results: Using porcine liver esterases, ~45% of the insect repellent was released over five days. Penetration and permeation studies of the copolymer and free repellent using excised, full-thickness porcine ear skin showed no detectable permeation of the copolymer through skin compared to the PMD. Moreover, tape stripping revealed that over 90% of the copolymer remained on the outer surface of the skin, whereas free PMD was within all skin layers. A planarian toxicity fluorescence assay indicated that that the copolymer is unlikely to be a significant irritant when applied topically. Conclusions: this study demonstrates the feasibility of the copolymer approach to develop extended-release insect repellents while reducing skin uptake and transdermal permeation of the small-molecular-weight active ingredient, in order to minimise any adverse effects. Full article
(This article belongs to the Special Issue Recent Developments in Polymer–Drug Conjugates)
►▼ Show Figures

Figure 1

17 pages, 3171 KiB  
Article
Polymer Pro-Drug Nanoparticles for Sustained Release of Cytotoxic Drugs Evaluated in Patient-Derived Glioblastoma Cell Lines and In Situ Gelling Formulations
by Catherine E. Vasey, Robert J. Cavanagh, Vincenzo Taresco, Cara Moloney, Stuart Smith, Ruman Rahman and Cameron Alexander
Pharmaceutics 2021, 13(2), 208; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020208 - 03 Feb 2021
Cited by 14 | Viewed by 3189
Abstract
Glioblastoma (GBM) is the most common, malignant and aggressive brain tumour in adults. Despite the use of multimodal treatments, involving surgery, followed by concomitant radiotherapy and chemotherapy, the median survival for patients remains less than 15 months from diagnosis. Low penetration of drugs [...] Read more.
Glioblastoma (GBM) is the most common, malignant and aggressive brain tumour in adults. Despite the use of multimodal treatments, involving surgery, followed by concomitant radiotherapy and chemotherapy, the median survival for patients remains less than 15 months from diagnosis. Low penetration of drugs across the blood-brain barrier (BBB) is a dose-limiting factor for systemic GBM therapies, and as a result, post-surgical intracranial drug delivery strategies are being developed to ensure local delivery of drugs within the brain. Here we describe the effects of PEGylated poly(lactide)-poly(carbonate)-doxorubicin (DOX) nanoparticles (NPs) on the metabolic activity of primary cancer cell lines derived from adult patients following neurosurgical resection, and the commercially available GBM cell line, U87. The results showed that non-drug-loaded NPs were well tolerated at concentrations of up to 100 µg/mL while tumour cell-killing effects were observed for the DOX-NPs at the same concentrations. Further experiments evaluated the release of DOX from polymer-DOX conjugate NPs when incorporated in a thermosensitive in situ gelling poly(DL-lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) matrix paste, in order to simulate the clinical setting of a locally injected formulation for GBM following surgical tumour resection. These assays demonstrated drug release from the polymer pro-drugs, when in PLGA/PEG matrices of two formulations, over clinically relevant time scales. These findings encourage future in vivo assessment of the potential capability of polymer–drug conjugate NPs to penetrate brain parenchyma efficaciously, when released from existing interstitial delivery systems. Full article
(This article belongs to the Special Issue Recent Developments in Polymer–Drug Conjugates)
►▼ Show Figures

Figure 1

19 pages, 4018 KiB  
Article
Synthesis and Characterization of pH-Sensitive Inulin Conjugate of Isoniazid for Monocyte-Targeted Delivery
by Franklin Afinjuomo, Thomas G. Barclay, Ankit Parikh, Rosa Chung, Yunmei Song, Gayathri Nagalingam, Jamie Triccas, Lixin Wang, Liang Liu, John D. Hayball, Nikolai Petrovsky and Sanjay Garg
Pharmaceutics 2019, 11(11), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11110555 - 28 Oct 2019
Cited by 17 | Viewed by 3720
Abstract
The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the [...] Read more.
The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment. Full article
(This article belongs to the Special Issue Recent Developments in Polymer–Drug Conjugates)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop