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Polymeric Nanoparticles for Drug Delivery and Diagnostics

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A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (25 February 2019) | Viewed by 30850

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Special Issue Editors

Prof. Dr. Kris Thurecht

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Guest Editor

1. Centre for Advanced Imaging and Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
2. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and ARC Training Centre for Innovation in Biomedical Imaging Technology, The University of Queensland, St Lucia, QLD 4072, Australia
Interests: molecular imaging; polymer chemistry; multimodal imaging; theranostics; drug delivery; nanomedicine
Special Issues, Collections and Topics in MDPI journals

Dr. Georgina Such

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Guest Editor

Department of Chemistry, University of Melbourne, Parkville, VIC 3010, Australia
Interests: stimuli-responsive nanoparticles; drug delivery; endosomal escape
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polymers play an increasingly important role in next generation therapeutics and diagnostics. Their intrinsic properties have allowed the development of new nanomedicines that not only allow for improved accumulation and delivery of therapeutic and or diagnostic agents to diseases, but also provide routes to better understand the mechanism of disease. While there are countless examples of polymeric therapeutics and diagnostics that have shown great promise in the preclinical assessment phase, their translation to clinical trials or acceptance in medicine have been limited to a handful of examples. This exemplifies the clear deficiencies in our understanding of how such materials interact and behave under biological conditions, and the challenges that face the field.

This Special Issue aims to investigate the different role that polymers play in the nanomedicine sphere, with a focus on investigating the effect of chemistry, morphology, architecture and assembly on the behaviour of polymer nanoparticles in biological settings. This could include assessment and validation of specific systems using in vitro, in vivo or ex vivo models of disease. Ideally, contributions should provide insight into how new polymer design or formulations contribute to our understanding of the polymer-biology interface. Both original contributions and reviews are welcome to provide a clear picture of the current state-of-the-art in polymer therapeutics and diagnostics.

Assoc. Prof. Kris Thurecht
Dr. Georgina Such
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. Polymers is an international peer-reviewed open access semimonthly 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 2700 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 therapeutics
Drug delivery
Theranostics
Polymer diagnostics
Nanomedicine
Polymer biology interface
Polymer chemistry

Published Papers (7 papers)

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Research

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11 pages, 1617 KiB

Open AccessArticle

Marine Bacterial Exopolymers-Mediated Green Synthesis of Noble Metal Nanoparticles with Antimicrobial Properties

by Angela Scala, Anna Piperno, Alexandru Hada, Simion Astilean, Adriana Vulpoi, Giovanna Ginestra, Andreana Marino, Antonia Nostro, Vincenzo Zammuto and Concetta Gugliandolo

Polymers 2019, 11(7), 1157; https://doi.org/10.3390/polym11071157 - 07 Jul 2019

Cited by 27 | Viewed by 3780

Abstract

A straightforward and green method for the synthesis of gold, silver, and silver chloride nanoparticles (Au NPs and Ag/AgCl NPs) was developed using three different microbial exopolymers (EP) as reducing and stabilizing agents. The exopolysaccharides EPS B3-15 and EPS T14 and the poly-γ-glutamic acid γ-PGA-APA were produced by thermophilic bacteria isolated from shallow hydrothermal vents off the Eolian Islands (Italy) in the Mediterranean Sea. The production of metal NPs was monitored by UV−Vis measurements by the typical plasmon resonance absorption peak and their antimicrobial activity towards Gram-positive and Gram- negative bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), as well as fungi (Candida albicans) was investigated. The biological evaluation showed no activity for EP-Au NPs, except against E. coli, whereas EP-Ag NPs exhibited a broad-spectrum of activity. The chemical composition, morphology, and size of EP-Ag NPs were investigated by UV–Vis, zeta potential (ζ), dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM). The best antimicrobial results were obtained for EPS B3-15-Ag NPs and EPS T14-Ag NPs (Minimum Inhibitory Concentration, MIC: 9.37–45 µg/mL; Minimum Bactericidal Concentration/Minimum Fungicidal Concentration, MBC/MFC: 11.25–75 µg/mL). Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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13 pages, 858 KiB

Open AccessArticle

Hydrodynamic Properties of Polymers Screening the Electrokinetic Flow: Insights from a Computational Study

by Peng Wu, Tao Sun, Xikai Jiang and Svyatoslav Kondrat

Polymers 2019, 11(6), 1038; https://doi.org/10.3390/polym11061038 - 11 Jun 2019

Cited by 4 | Viewed by 3252

Abstract

Understanding the hydrodynamic properties of polymeric coatings is crucial for the rational design of molecular transport involving polymeric surfaces and is relevant to drug delivery, sieving, molecular separations, etc. It has been found that the hydrodynamic radius of a polymer segment is an order of magnitude smaller than its physical size, but the origin of this effect does not seem to be well understood. Herein, we study the hydrodynamic properties of polymeric coatings by using molecular dynamics simulations, navigated by the continuous Navier-Stokes-Brinkman model. We confirm that the averaged hydrodynamic radius of a polymer bead is about one order of magnitude smaller than its physical radius, and, in addition, we show that it exhibits a strong dependence on the degree of polymerization. We relate this variation of the hydrodynamic radius to the structural properties and hydrodynamic shielding by surrounding polymer beads. This is done by separating the effects originating from near and far beads. For the near beads, shielding is mainly due to the two nearest beads (of the same polymer) and leads to about a 5-fold reduction in the hydrodynamic radius. Assuming the additivity of the hydrodynamic shielding by far beads, we suggest a simple model, which captures correctly the qualitative behaviour of the hydrodynamic radius with the degree of polymerization. The revealed shielding effects provide important insights relevant to the advanced modelling of hydrodynamic properties of polymeric coatings. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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12 pages, 3917 KiB

Open AccessArticle

Receptor-mediated Uptake of Folic Acid-functionalized Dextran Nanoparticles for Applications in Photodynamic Therapy

by Kathrin Butzbach, Matthias Konhäuser, Matthias Fach, Denise N. Bamberger, Benjamin Breitenbach, Bernd Epe and Peter R. Wich

Polymers 2019, 11(5), 896; https://doi.org/10.3390/polym11050896 - 16 May 2019

Cited by 24 | Viewed by 4961

Abstract

In photodynamic therapy (PDT), photosensitizers and light are used to cause photochemically induced cell death. The selectivity and the effectiveness of the phototoxicity in cancer can be increased by a specific uptake of the photosensitizer into tumor cells. A promising target for this goal is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe a polysaccharide-based nanoparticle system suitable for targeted uptake and its photochemical and photobiological characterization. The photosensitizer 5, 10, 15, 20-tetraphenyl-21H, 23H-porphyrine (TPP) was encapsulated in spermine- and acetal-modified dextran (SpAcDex) nanoparticles and conjugated with folic acid (FA) on the surface [SpAcDex(TPP)-FA]. The particles are successfully taken up by human HeLa-KB cells, and a light-induced cytotoxicity is observable. An excess of free folate as the competitor for the FRα-mediated uptake inhibits the phototoxicity. In conclusion, folate-modified SpAcDex particles are a promising drug delivery system for a tumor cell targeted photodynamic therapy. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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15 pages, 9872 KiB

Open AccessArticle

Co-Encapsulation and Co-Delivery of Peptide Drugs via Polymeric Nanoparticles

by Ma Rie Kim, Teng Feng, Qian Zhang, Ho Yin Edwin Chan and Ying Chau

Polymers 2019, 11(2), 288; https://doi.org/10.3390/polym11020288 - 08 Feb 2019

Cited by 15 | Viewed by 6002

Abstract

Combination therapy is a promising form of treatment. In particular, co-treatment of P3 and QBP1 has been shown to enhance therapeutic effect in vivo in treating polyglutamine diseases. These peptide drugs, however, face challenges in clinical administration due to poor stability, inability to reach intracellular targets, and lack of method to co-deliver both drugs. Here we demonstrate two methods of co-encapsulating the peptide drugs via polymer poly(ethylene glycol)-block-polycaprolactone (PEG-b-PCL) based nanoparticles. Nanoparticles made by double emulsion were 100–200 nm in diameter, with drug encapsulation efficiency of around 30%. Nanoparticles made by nanoprecipitation with lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) were around 250–300 nm in diameter, with encapsulation efficiency of 85–100%. Particles made with both formulations showed cellular uptake when decorated with a mixture of peptide ligands that facilitate endocytosis. In vitro assay showed that nanoparticles could deliver bioactive peptides and encapsulation by double emulsion were found to be more effective in rescuing cells from polyglutamine-induced toxicity. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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13 pages, 3228 KiB

Open AccessArticle

Noncovalent Complexation of Amphotericin B with Poly(β-Amino Ester) Derivates for Treatment of C. Neoformans Infection

by Yang Yu, Li Peng, Guojian Liao, Zhangbao Chen and Chong Li

Polymers 2019, 11(2), 270; https://doi.org/10.3390/polym11020270 - 05 Feb 2019

Cited by 6 | Viewed by 2907

Abstract

Our goal was to improve treatment outcomes for C. neoformans infection by designing nanocarriers that enhance drug-encapsulating capacity and stability. Thus, a noncovalent complex of methoxy poly(ethylene glycol)-poly(lactide)-poly(β-amino ester) (MPEG-PLA-PAE) and amphotericin B (AMB) was developed and characterized. The MPEG-PLA-PAE copolymer was synthesized by a Michael-type addition reaction; the copolymer was then used to prepare the AMB-loaded nanocomplex. AMB was in a highly aggregated state within complex cores. A high encapsulation efficiency (>90%) and stability of the AMB-loaded nanocomplex were obtained via electrostatic interaction between AMB and PAE blocks. This nanocomplex retained drug activity against C. neoformans in vitro. Compared with micellar AMB, the AMB nanocomplex was more efficient in terms of reducing C. neoformans burden in lungs, liver, and spleen, based on its improved biodistribution. The AMB/MPEG-PLA-PAE complex with enhanced drug-loading capacity and stability can serve as a platform for effective treatment of C. neoformans infection. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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Review

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33 pages, 2264 KiB

Open AccessReview

Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface

by Joshua D Simpson, Samuel A Smith, Kristofer J. Thurecht and Georgina Such

Polymers 2019, 11(9), 1441; https://doi.org/10.3390/polym11091441 - 02 Sep 2019

Cited by 24 | Viewed by 4444

Abstract

Nanomedicine has generated significant interest as an alternative to conventional cancer therapy due to the ability for nanoparticles to tune cargo release. However, while nanoparticle technology has promised significant benefit, there are still limited examples of nanoparticles in clinical practice. The low translational success of nanoparticle research is due to the series of biological roadblocks that nanoparticles must migrate to be effective, including blood and plasma interactions, clearance, extravasation, and tumor penetration, through to cellular targeting, internalization, and endosomal escape. It is important to consider these roadblocks holistically in order to design more effective delivery systems. This perspective will discuss how nanoparticles can be designed to migrate each of these biological challenges and thus improve nanoparticle delivery systems in the future. In this review, we have limited the literature discussed to studies investigating the impact of polymer nanoparticle structure or composition on therapeutic delivery and associated advancements. The focus of this review is to highlight the impact of nanoparticle characteristics on the interaction with different biological barriers. More specific studies/reviews have been referenced where possible. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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34 pages, 916 KiB

Open AccessEditor’s ChoiceReview

Delivering Combination Chemotherapies and Targeting Oncogenic Pathways via Polymeric Drug Delivery Systems

by Praful R. Nair

Polymers 2019, 11(4), 630; https://doi.org/10.3390/polym11040630 - 05 Apr 2019

Cited by 26 | Viewed by 4852

Abstract

The side-effects associated with chemotherapy necessitates better delivery of chemotherapeutics to the tumor. Nanoparticles can load higher amounts of drug and improve delivery to tumors, increasing the efficacy of treatment. Polymeric nanoparticles, in particular, have been used extensively for chemotherapeutic delivery. This review describes the efforts made to deliver combination chemotherapies and inhibit oncogenic pathways using polymeric drug delivery systems. Combinations of chemotherapeutics with other drugs or small interfering RNA (siRNA) combinations have been summarized. Special attention is given to the delivery of drug combinations that involve either paclitaxel or doxorubicin, two popular chemotherapeutics in clinic. Attempts to inhibit specific pathways for oncotherapy have also been described. These include inhibition of oncogenic pathways (including those involving HER2, EGFR, MAPK, PI3K/Akt, STAT3, and HIF-1α), augmentation of apoptosis by inhibiting anti-apoptosis proteins (Bcl-2, Bcl-xL, and survivin), and targeting dysregulated pathways such as Wnt/β-catenin and Hedgehog. Full article

(This article belongs to the Special Issue Polymeric Nanoparticles for Drug Delivery and Diagnostics)

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