E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Polymers for Drug Delivery"

Quicklinks

A special issue of Polymers (ISSN 2073-4360).

Deadline for manuscript submissions: closed (30 November 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Gianfranco Pasut

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, Padova 35131, Italy
Website | E-Mail
Fax: +39 049 827 5366
Interests: polymer-drug and polymer-protein conjugates; PEGylation; enzymatic conjugation; site-selective polymer conjugation; enzymatic conjugation; tumor targeted anticancer conjugates; conjugates for combination therapy; hyaluronic acid as drug carrier; stealth liposomes

Special Issue Information

Dear Colleagues,

Polymers have performed and will continue to play a central role in drug delivery. These macromolecules are now being used in several drug delivery approaches (e.g., drug and protein conjugates, micro and nanoparticles, nanocapsules, matrices and hydrogels, polymersomes, complexing polymers etc.) or are themselves drugs (e.g., polymers for molecular sequestration). Polymers have, moreover, also been exploited to improve the performance of other drug delivery systems (e.g., stealth liposomes). In view of this vast scenario of applications, researchers continue to propose new polymers characterized by improved features and biocompatibility as well as innovative applications. Some have also been designed to successfully replace the current gold standard for stealth coatings, polyethylene glycol (PEG). The sum of these research activities has yielded a growing number of polymer-based products that have been approved by regulatory authorities or are under investigation in clinical trials.

Relevant, “smart” carriers are needed to recapture the interest of the pharmaceutical industry which has the means to cover research costs to develop new polymers for human use. Collaboration between academia and the pharmaceutical industry must be promoted if research findings in the laboratory are to be taken to the bedside. As researchers design new studies in this field, it is important that they address vital issues such as reproducible synthesis, biodegradability of polymers, elimination pathways, biocompatibility, storage stability, polydispersity, polymer characterization methods, feasibility of selective chemical modification, etc.

This issue aims to review the current state-of-the-art concerning polymeric drug delivery systems and to envision future perspectives. The topical subjects to be addressed include: synthetic polymers, natural polymers, bioconjugation of polymers, smart polymers, amphiphilic polymers, bioactive polymers, the dynamics of polymers crossing biological barriers, targeted drug delivery, polymers as drugs, etc.

Prof. Dr. Gianfranco Pasut
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers 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 1400 CHF (Swiss Francs).


Keywords

  • drug delivery
  • bio-responsive polymers
  • biocompatible polymers
  • amphiphilic polymers
  • dendrimers
  • smart polymers

Published Papers (12 papers)

View options order results:
result details:
Displaying articles 1-12
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates
Polymers 2014, 6(8), 2186-2220; doi:10.3390/polym6082186
Received: 19 February 2014 / Revised: 28 June 2014 / Accepted: 14 July 2014 / Published: 20 August 2014
Cited by 4 | PDF Full-text (1515 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polymer-drug conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-drug conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive
[...] Read more.
Polymer-drug conjugates have demonstrated clinical potential in the context of anticancer therapy. However, such promising results have, to date, failed to translate into a marketed product. Polymer-drug conjugates rely on two factors for activity: (i) the presence of a defective vasculature, for passive accumulation of this technology into the tumour tissue (enhanced permeability and retention (EPR) effect) and (ii) the presence of a specific trigger at the tumour site, for selective drug release (e.g., the enzyme cathepsin B). Here, we retrospectively analyse literature data to investigate which tumour types have proved more responsive to polymer-drug conjugates and to determine correlations between the magnitude of the EPR effect and/or expression of cathepsin B. Lung, breast and ovarian cancers showed the highest response rate (30%, 47% and 41%, respectively for cathepsin-activated conjugates and 31%, 43%, 40%, across all conjugates). An analysis of literature data on cathepsin content in various tumour types showed that these tumour types had high cathepsin content (up to 3835 ng/mg for lung cancer), although marked heterogeneity was observed across different studies. In addition, these tumour types were also reported as having a high EPR effect. Our results suggest that a pre-screening of patient population could bring a more marked clinical benefit. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Open AccessArticle Preparation of Poly(acrylic acid) Hydrogel by Radiation Crosslinking and Its Application for Mucoadhesives
Polymers 2014, 6(3), 890-898; doi:10.3390/polym6030890
Received: 8 January 2014 / Revised: 7 March 2014 / Accepted: 13 March 2014 / Published: 19 March 2014
Cited by 12 | PDF Full-text (264 KB) | HTML Full-text | XML Full-text
Abstract
A mucoadhesive drug delivery system can improve the effectiveness of a drug by maintaining the drug concentration and allowing targeting and localization of the drug at a specific site. Acrylic-based hydrogels have been used extensively as a mucoadhesive system owing to their flexibility
[...] Read more.
A mucoadhesive drug delivery system can improve the effectiveness of a drug by maintaining the drug concentration and allowing targeting and localization of the drug at a specific site. Acrylic-based hydrogels have been used extensively as a mucoadhesive system owing to their flexibility and excellent bioadhesion. In this experiment, poly(acrylic acid) was selected to prepare the bioadhesive hydrogel adhering to mucosal surfaces using a radiation process. Poly(acrylic acid) was dissolved in water to a prepare poly(acrylic acid) solution, and the solution was then irradiated by an electron beam at up to 75 kGy to make hydrogels. Their physical properties, such as gel percent, swelling percent and adhesive strength to mucosal surfaces, were investigated. Triamcinolone acetonide was used as a model drug. The dried poly(acrylic acid) film was dipped in a 0.1 wt% triamcinolone acetonide solution in ethanol, and then dried at 25 °C. The release of triamcinolone acetonide was determined at different time intervals, and UV (Ultraviolet)-Vis spectroscopy was used to determine the released concentration of triamcinolone acetonide at 238 nm. It was shown that poly(acrylic acid)-based drug carriers were successfully prepared for use in a bioadhesive drug delivery system. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Open AccessArticle Antimicrobial Plant Extracts Encapsulated into Polymeric Beads for Potential Application on the Skin
Polymers 2014, 6(2), 479-490; doi:10.3390/polym6020479
Received: 12 December 2013 / Revised: 4 February 2014 / Accepted: 10 February 2014 / Published: 18 February 2014
Cited by 12 | PDF Full-text (297 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the in vitro bacterial growth inhibition, antioxidant activity and the content in bioactive components of Plectranthus barbatus, P. hadiensis var. tomentosus, P. madagascarensis, P. neochilus and P. verticillatus aqueous extracts were investigated and compared by three extraction methods
[...] Read more.
In this study, the in vitro bacterial growth inhibition, antioxidant activity and the content in bioactive components of Plectranthus barbatus, P. hadiensis var. tomentosus, P. madagascarensis, P. neochilus and P. verticillatus aqueous extracts were investigated and compared by three extraction methods (infusion, decoction and microwave extractions). The microwave extract of P. madagascariensis showed the higher antimicrobial activity against the Staphylococcus epidermidis strain with a minimum inhibitory concentration of 40 µg/mL. This extract also showed no toxicity in a general toxicity assay and no considerable cytotoxicity against a human keratinocyte cell line. The antioxidant activity of the extracts was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH method), and all showed antioxidant activity. The microwave extract of P. madagascariensis was the one with the highest antioxidant activity (IC50 value of 41.66 µg/mL). To increase extract stability, the microwave P. madagascariensis extract was then successfully encapsulated into alginate beads with high efficiency. This effective and low-cost strategy seems to be easy to extrapolate to an industrial scale with a future application on the skin. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Open AccessArticle RGD-Functionalization of Poly(2-oxazoline)-Based Networks for Enhanced Adhesion to Cancer Cells
Polymers 2014, 6(2), 264-279; doi:10.3390/polym6020264
Received: 16 November 2013 / Revised: 8 January 2014 / Accepted: 15 January 2014 / Published: 27 January 2014
Cited by 8 | PDF Full-text (3646 KB) | HTML Full-text | XML Full-text
Abstract
Poly(2-oxazoline) networks with varying swelling degrees and varying hydrophilicity can be synthesized from 2-ethyl-2-oxazoline, 2-nonyl-2-oxazoline, 2-9’-decenyl-2-oxazoline and 2,2’-tetramethylene-bis-2-oxazoline in one-pot/one-step strategies. These gels can be loaded with organic molecules, such as fluorescein isothiocyanate, either during the polymerization (covalent attachment of the dye) or
[...] Read more.
Poly(2-oxazoline) networks with varying swelling degrees and varying hydrophilicity can be synthesized from 2-ethyl-2-oxazoline, 2-nonyl-2-oxazoline, 2-9’-decenyl-2-oxazoline and 2,2’-tetramethylene-bis-2-oxazoline in one-pot/one-step strategies. These gels can be loaded with organic molecules, such as fluorescein isothiocyanate, either during the polymerization (covalent attachment of the dye) or according to post-synthetic swelling/deswelling strategies (physical inclusion of the dye). Surface functionalization of ground gels by thiol-ene reactions with cysteine-bearing peptides exhibiting the arginine-glycine-aspartic acid (RGD) motif yields microparticles with enhanced recognition of human cancer cells compared to healthy endothelial cells. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Open AccessArticle Biocompatibility of Poly(ester amide) (PEA) Microfibrils in Ocular Tissues
Polymers 2014, 6(1), 243-260; doi:10.3390/polym6010243
Received: 30 November 2013 / Revised: 10 January 2014 / Accepted: 13 January 2014 / Published: 21 January 2014
Cited by 6 | PDF Full-text (2779 KB) | HTML Full-text | XML Full-text
Abstract
Drug delivery systems (DDS) are able to deliver, over long periods of time, therapeutic concentrations of drugs requiring frequent administration. Two classes of DDS are available, biodegradable and non-biodegradable. The larger non-biodegradable implants ensure long-term delivery, but require surgical interventions. Biodegradable biomaterials are
[...] Read more.
Drug delivery systems (DDS) are able to deliver, over long periods of time, therapeutic concentrations of drugs requiring frequent administration. Two classes of DDS are available, biodegradable and non-biodegradable. The larger non-biodegradable implants ensure long-term delivery, but require surgical interventions. Biodegradable biomaterials are smaller, injectable implants, but degrade hydrolytically and release drugs in non-zero order kinetics, which is inefficient for long-term sustained drug release. Biodegradable poly(ester amides) (PEAs) may overcome these difficulties. To assess their ocular biocompatibility and long-term behavior, PEA fibrils were analyzed in vitro and in vivo. In vitro, incubation in vitreous humor changes to PEA structure, suggests degradation by surface erosion, enabling drug release with zero order kinetics. Clinical and histological analysis of PEA fibrils implanted subconjunctivally and intravitreally showed the absence of an inflammatory response or other pathological tissue alteration. This study shows that PEA fibrils are biocompatible with ocular environment and degrade by surface erosion. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Open AccessArticle Synthesis of Gelatin-γ-Polyglutamic Acid-Based Hydrogel for the In Vitro Controlled Release of Epigallocatechin Gallate (EGCG) from Camellia sinensis
Polymers 2014, 6(1), 39-58; doi:10.3390/polym6010039
Received: 31 October 2013 / Revised: 12 December 2013 / Accepted: 16 December 2013 / Published: 27 December 2013
Cited by 10 | PDF Full-text (946 KB) | HTML Full-text | XML Full-text
Abstract
The antioxidant property and other health benefits of the most abundant catechin, epigallocatechin gallate (EGCG), are limited because of poor stability and permeability across intestine. Protecting the EGCG from the harsh gastrointestinal tract (GIT) environment can help to increase its bioavailability following oral
[...] Read more.
The antioxidant property and other health benefits of the most abundant catechin, epigallocatechin gallate (EGCG), are limited because of poor stability and permeability across intestine. Protecting the EGCG from the harsh gastrointestinal tract (GIT) environment can help to increase its bioavailability following oral administration. In this study, EGCG was loaded to hydrogel prepared from ionic interaction between an optimized concentration of gelatin and γ-polyglutamic acid (γ-PGA), with ethylcarbodiimide (EDC) as the crosslinker. Physicochemical characterization of hydrogel was done using Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The dependence of the swelling degree (SD) of the hydrogel to the amount of gelatin, γ-PGA, EDC, swelling time and pH was determined. A high SD of the crosslinked hydrogel was noted at pH 4.5, 6.8 and 9.0 compared to pH 7.4, which describes pH-responsiveness. Approximately 67% of the EGCG from the prepared solution was loaded to the hydrogel after 12 h post-loading, in which loading efficiency was related to the amount of EDC. The in vitro release profile of EGCG at pH 1.2, 6.8 and 7.4, simulating GIT conditions, resulted in different sustained release curves. Wherein, the released EGCG was not degraded instantly compared to free-EGCG at controlled temperature of 37 °C at different pH monitored against time. Therefore, this study proves the potential of pH-responsive gelatin-γ-PGA-based hydrogel as a biopolymer vehicle to deliver EGCG. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Review

Jump to: Research

Open AccessReview Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities
Polymers 2014, 6(3), 799-819; doi:10.3390/polym6030799
Received: 31 January 2014 / Revised: 2 March 2014 / Accepted: 3 March 2014 / Published: 13 March 2014
Cited by 6 | PDF Full-text (454 KB) | HTML Full-text | XML Full-text
Abstract
Osteoarthritis (OA) is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce
[...] Read more.
Osteoarthritis (OA) is a big burden of disease worldwide and one of the most common causes of disability in the adult population. Currently applied therapies consist of physical therapy, oral medication, intra-articular injections, and surgical interventions, with the main goal being to reduce pain and improve function and quality of life. Intra-articular (IA) administration of drugs has potential benefits in OA treatment because it minimizes systemic bioavailability and side effects associated with oral administration of drugs without compromising the therapeutic effect in the joint. However, IA drug residence time is short and there is a clinical need for a vehicle that is able to provide a sustained release long enough for IA therapy to fulfill its promise. This review summarizes the use of different polymeric systems and the incorporated drugs for IA drug delivery in the osteoarthritic joint with a primary focus on clinical needs and opportunities. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Open AccessReview Local Delivery of Antiproliferative Agents via Stents
Polymers 2014, 6(3), 755-775; doi:10.3390/polym6030755
Received: 2 December 2013 / Revised: 10 February 2014 / Accepted: 25 February 2014 / Published: 12 March 2014
Cited by 2 | PDF Full-text (2011 KB) | HTML Full-text | XML Full-text
Abstract
A stent is a medical device for serving as an internal scaffold to maintain or increase the lumen of a body conduit. Stent placement has become a primary treatment option in coronary artery disease for more than the last two decades. The stenting
[...] Read more.
A stent is a medical device for serving as an internal scaffold to maintain or increase the lumen of a body conduit. Stent placement has become a primary treatment option in coronary artery disease for more than the last two decades. The stenting is also currently used for relieving the symptoms of narrowed lumen of nonvascular organs, such as esophagus, trachea and bronchi, small and large intestines, biliary, and urinary tract. Local delivery of active pharmaceutical agents via the stents can not only enhance healing of certain diseases, but it can also help decrease the potential risk of the stenting procedure to the surrounding tissue. In this review, we focus on reviewing a variety of drug-impregnated stents and local drug delivery systems using the stents. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Open AccessReview Peptide-Based Polymer Therapeutics
Polymers 2014, 6(2), 515-551; doi:10.3390/polym6020515
Received: 28 December 2013 / Revised: 6 February 2014 / Accepted: 7 February 2014 / Published: 21 February 2014
Cited by 18 | PDF Full-text (1090 KB) | HTML Full-text | XML Full-text
Abstract
Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical
[...] Read more.
Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Open AccessReview Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules
Polymers 2014, 6(2), 346-369; doi:10.3390/polym6020346
Received: 3 December 2013 / Revised: 22 January 2014 / Accepted: 23 January 2014 / Published: 30 January 2014
Cited by 34 | PDF Full-text (794 KB) | HTML Full-text | XML Full-text
Abstract
Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or
[...] Read more.
Hyaluronic acid (HA) has currently several therapeutic applications: in ophthalmology, osteoarthritis, wound healing, tissue regeneration, postoperative anti-adhesion and anesthetic medicine. In the last ten years, it has also been successfully investigated in the field of drug delivery, in the form of conjugates or hydrogel depot systems. HAylation, the covalent conjugation of HA to bioactive molecules, allows the overcoming of disadvantages associated with some pharmaceuticals, such as insolubility, instability and fast kidney clearance. These issues can be addressed also by covalent attachment of polyethylene glycol (PEGylation), but HA has the relevant advantages of biodegradability, high loading and specific targeting. In this review, the novel HA derivatives and the latest advances in HA-based drug delivery with a particular focus on the chemistry of conjugation will be discussed. Although, so far, there are no HA-drug conjugates on the market, several derivatives are presently under clinical investigation, and the promising results encourage further investigations and the exploitation of this versatile polysaccharide. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Open AccessReview Polyester Dendrimers: Smart Carriers for Drug Delivery
Polymers 2014, 6(1), 179-213; doi:10.3390/polym6010179
Received: 29 November 2013 / Revised: 3 January 2014 / Accepted: 8 January 2014 / Published: 15 January 2014
Cited by 12 | PDF Full-text (1145 KB) | HTML Full-text | XML Full-text
Abstract
Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug
[...] Read more.
Polyester dendrimers have been shown to be outstanding candidates for biomedical applications. Compared to traditional polymeric drug vehicles, these biodegradable dendrimers show excellent advantages especially as drug delivery systems because they are non-toxic. Here, advances on polyester dendrimers as smart carriers for drug delivery applications have been surveyed. Both covalent and non-covalent incorporation of drugs are discussed. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)
Figures

Open AccessReview Polymers for Protein Conjugation
Polymers 2014, 6(1), 160-178; doi:10.3390/polym6010160
Received: 3 December 2013 / Revised: 30 December 2013 / Accepted: 7 January 2014 / Published: 13 January 2014
Cited by 15 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
Polyethylene glycol (PEG) at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers
[...] Read more.
Polyethylene glycol (PEG) at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones. Full article
(This article belongs to the Special Issue Polymers for Drug Delivery)

Journal Contact

MDPI AG
Polymers Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
polymers@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Polymers
Back to Top