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Polymers and Drug Delivery Systems

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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 (31 March 2021) | Viewed by 53486

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Prof. Dr. Iolanda De Marco

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Industrial Engineering Department, University of Salerno, Via Giovanni Paolo II, 132, I-84084 Fisciano, SA, Italy
Interests: polymer/active principle composites; drug delivery; supercritical carbon dioxide; microparticles and nanoparticles precipitation; biopolymer aerogels; polymer/drug coprecipitation
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Dear Colleagues,

Biocompatible natural and synthetic polymers are commonly used for drug delivery. Depending on the specific application, a modified release of the drug is frequently required, considering that the bioavailability of the active principal depends on its dissolution rate. If an active principal is scarcely soluble in water and a fast release is required, a hydrosoluble polymer can be used as carrier for the drug to enhance its dissolution rate. Contrariwise, controlled or sustained drug release obtained with the aid of hydrophobic polymers can be used to extend the active principle release, reducing the number of administrations. Additionally, the release of the drug at or near a specific site of action can be reached with targeted release products. In all these novel formulations, the characteristics of the final product strongly depend on the choice of the polymeric carrier.

The aim of this Special Issue is to collect research and review papers on different polymer/drug composites. Polymer/drug microparticles to obtain tablets or granules for oral suspensions, polymeric capsules containing the active principle, loaded foams, membranes, or aerogels for topical delivery are welcome.

Prof. Dr. Iolanda De Marco
Guest Editor

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Keywords

polymer/drug composites
fast, controlled or prolonged release
targeted delivery
natural and synthetic polymers
bioavailability
coprecipitated microparticles
drug loaded aerogels and foams
capsules for active principle delivery

Published Papers (12 papers)

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Research

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15 pages, 3369 KiB

Open AccessArticle

Formation of Rutin–β-Cyclodextrin Inclusion Complexes by Supercritical Antisolvent Precipitation

by Paola Franco and Iolanda De Marco

Polymers 2021, 13(2), 246; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13020246 - 13 Jan 2021

Cited by 19 | Viewed by 2158

Abstract

In this work, rutin (RUT)–β-cyclodextrin (β-CD) inclusion complexes are prepared by Supercritical AntiSolvent (SAS) precipitation. Well-defined composite microparticles are obtained at guest:host ratios equal to 1:2 and 1:1 mol:mol. The dimensions of composite particles range between 1.45 ± 0.88 µm and 7.94 ± 2.12 µm. The formation of RUT–β-CD inclusion complexes has been proved by different analyses, including Fourier transform infrared spectroscopy, Differential Scanning Calorimetry, X-ray diffraction, and UV-vis spectroscopy. The dissolution tests reveal a significant improvement in the release rate of RUT from inclusion complexes. Indeed, compared to the unprocessed RUT, the dissolution rate is about 3.9 and 2.4 times faster in the case of the complexes RUT–β-CD 1:2 and 1:1 mol:mol, respectively. From a pharmaceutical/nutraceutical point of view, CD-based inclusion complexes allow the reduction of the polymer amount in the SAS composite formulations. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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14 pages, 2993 KiB

Open AccessArticle

Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

by Elad Hadad, Safra Rudnick-Glick, Ella Itzhaki, Matan Y. Avivi, Igor Grinberg, Yuval Elias and Shlomo Margel

Polymers 2020, 12(12), 2996; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12122996 - 16 Dec 2020

Cited by 7 | Viewed by 2202

Abstract

Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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14 pages, 2360 KiB

Open AccessArticle

Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route

by Nikesh Shrestha, Saba Khan, Yub Raj Neupane, Shweta Dang, Shadab Md, Usama A. Fahmy, Sabna Kotta, Nabil A. Alhakamy, Sanjula Baboota and Javed Ali

Polymers 2020, 12(11), 2589; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12112589 - 04 Nov 2020

Cited by 7 | Viewed by 2263

Abstract

In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (C_max 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC_0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (C_max 245.44 ± 12.83 ng/mL, t_max 1 h, and AUC_0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (C_max 211.67 ± 12.82, t_max 2 h, and AUC_0-480 1036.78 ng.min/mL). The brain–blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood–brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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14 pages, 7272 KiB

Open AccessArticle

Poly (Lactic-co-Glycolic Acid) Nanoparticles and Nanoliposomes for Protein Delivery in Targeted Therapy: A Comparative In Vitro Study

by Giulia De Negri Atanasio, Pier Francesco Ferrari, Roberta Campardelli, Patrizia Perego and Domenico Palombo

Polymers 2020, 12(11), 2566; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12112566 - 01 Nov 2020

Cited by 14 | Viewed by 3031

Abstract

Over the previous years, the design, development, and potential application of nanocarriers in the medical field have been intensively studied for their ability to preserve drug properties, especially their pharmacological activity, and to improve their bioavailability. This work is a comparative study between two different types of nanocarriers, poly (lactic-co-glycolic acid)-based nanoparticles and phosphatidylcholine-based nanoliposomes, both prepared for the encapsulation of bovine serum albumin as a model protein. Polymeric nanoparticles were produced using the double emulsion water-oil-water evaporation method, whereas nanoliposomes were obtained by the thin-film hydration method. Both nanocarriers were characterized by morphological analysis, particle mean size, particle size distribution, and protein entrapment efficiency. Invitro release studies were performed for 12 days at 37 °C. In order to explore a possible application of these nanocarriers for a targeted therapy in the cardiovascular field, hemolytic activity and biocompatibility, in terms of cell viability, were performed by using human red blood cells and EA.hy926 human endothelial cell line, respectively. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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17 pages, 4293 KiB

Open AccessArticle

Highly Enhanced Curcumin Delivery Applying Association Type Nanostructures of Block Copolymers, Cyclodextrins and Polycyclodextrins

by Nóra Zsuzsanna Nagy, Zoltán Varga, Judith Mihály, Attila Domján, Éva Fenyvesi and Éva Kiss

Polymers 2020, 12(9), 2167; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12092167 - 22 Sep 2020

Cited by 9 | Viewed by 2886

Abstract

The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four Pluronics (94, 105, 127,108) with different compositions led to the conclusion that solubilization capacity is maximum for Pluronic 105 with intermediate polarity (hydrophilic/lipophilic balance (HLB) = 15) possessing the optimum balance between capacity of hydrophobic core of the micelle and hydrophilic stabilizing shell of the associate. Curcumin concentration in aqueous solution was managed to increase 105 times up to 1–3 g/L applying Pluronic at 0.01 mol/L. Formation of a host–guest complex of cyclodextrin as another way of increasing the curcumin solubility was also tested. Comparing the(2-hydroxypropyl)-α, β and γ cyclodextrins (CD) with 6, 7 and 8 sugar units and their polymers (poly-α-CD, poly-β-CD, poly-γ-CD) the γ-CD with the largest cavity found to be the most effective in curcumin encapsulation approaching the g/L range of concentration. The polymer type of the CDs presented prolonged and pH dependent release of curcumin in the gastrointestinal (GI) system modelled by simulated liquids. This retarding effect of polyCD was also shown and can be used for tuning in the combined system of Pluronic micelle and polyCD where the curcumin release was slower than from the micelle. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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17 pages, 3017 KiB

Open AccessArticle

Novel Histone-Based DNA Carrier Targeting Cancer-Associated Fibroblasts

by Alexey Kuzmich, Olga Rakitina, Dmitry Didych, Victor Potapov, Marina Zinovyeva, Irina Alekseenko and Eugene Sverdlov

Polymers 2020, 12(8), 1695; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12081695 - 29 Jul 2020

Cited by 8 | Viewed by 2867

Abstract

Nuclear proteins, like histone H2A, are promising non-viral carriers for gene delivery since they are biocompatible, biodegradable, bear intrinsic nuclear localization signal, and are easy to modify. The addition of surface-protein-binding ligand to histone H2A may increase its DNA delivery efficiency. Tumor microenvironment (TME) is a promising target for gene therapy since its surface protein repertoire is more stable than that of cancer cells. Cancer-associated fibroblasts (CAFs) are important components of TME, and one of their surface markers is beta-type platelet-derived growth factor receptor (PDGFRβ). In this study, we fused histone H2A with PDGFRβ-binding peptide, YG2, to create a novel non-viral fibroblast-targeting DNA carrier, H2A-YG2. The transfection efficiency of histone complexes with pDNA encoding a bicistronic reporter (enhanced green fluorescent protein, EGFP, and firefly luciferase) in PDGFRβ-positive and PDGFRβ-negative cells was estimated by luciferase assay and flow cytometry. The luciferase activity, percentage of transfected cells, and overall EGFP fluorescence were increased due to histone modification with YG2 only in PDGFRβ-positive cells. We also estimated the internalization efficiency of DNA-carrier complexes using tetramethyl-rhodamine-labeled pDNA. The ligand fusion increased DNA internalization only in the PDGFRβ-positive cells. In conclusion, we demonstrated that the H2A-YG2 carrier targeted gene delivery to PDGFRβ-positive tumor stromal cells. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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13 pages, 2771 KiB

Open AccessArticle

Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen

by Munther Alomari, Rabindran Jermy Balasamy, Dana Almohazey, Vijaya Ravinayagam, Mohammad Al Hamad, Deena Ababneh, Hiba Bahmdan, Abdul-Hakeem Alomari, Zakaria Mokadem and Abdelhamid Elaissari

Polymers 2020, 12(7), 1516; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12071516 - 08 Jul 2020

Cited by 10 | Viewed by 3084

Abstract

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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10 pages, 5115 KiB

Open AccessArticle

Elaboration of Charged Poly(Lactic-co-Glycolic Acid) Microparticles for Effective Release of Tranexamic Acid

by Ming-Hsi Huang, Shun-Ying Huang, Yi-Xuan Chen, Cheng-You Chen and Yung-Sheng Lin

Polymers 2020, 12(4), 808; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12040808 - 04 Apr 2020

Cited by 2 | Viewed by 3348

Abstract

In this study, tranexamic acid (TA) was used as a model compound to study the charge effect on the physicochemical properties of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). Charged PLGA MPs were elaborated by the incorporation of a quaternary ammonium, cetyltrimethylammonium bromide (CTAB), during the double emulsion solvent evaporation process. Three TA-CTAB-carrying modes of PLGA MPs were designed in the CTAB-free (TA-MP), adsorption (TA-CTAB_AD), or encapsulation (TA-CTAB_EN) form. The obtained MPs were characterized by morphology and TA-MP affinity. The experiment revealed that the three prepared MPs were spherical and smooth, with pores on their surfaces. TA-CTAB_AD had a relatively narrow size distribution, compared with that of TA-MP and TA-CTAB_EN. The particle sizes of TA-MP, TA-CTAB_EN, TA-CTAB_AD were measured as 59 ± 17, 54 ± 20, and 19 ± 8 μm, respectively. The zeta potential of the three MPs was found to be in the order: TA-CTAB_AD > TA-CTAB_EN > TA-MP. Differential scanning calorimetry (DSC) indicated that the manufacturing process had no influence on the glass transition temperature of the MPs, which was close to 48 °C. Thermogravimetric analysis illustrated that the presence of CTAB slightly changed the thermal stability of PLGA MPs. In vitro release showed that TA-CTAB_AD exhibited faster TA release than TA-MP and TA-CTAB_EN in a basic environment (pH of 13), probably because of electrostatic attraction. At pH = 1, the release of TA from TA-CTAB_EN was faster than those from TA-MP and TA-CTAB_AD, probably because of electrostatic repulsion. However, the effect of electrostatic interaction was not significant at pH = 7.4. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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Review

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20 pages, 2129 KiB

Open AccessReview

Classification and Production of Polymeric Foams among the Systems for Wound Treatment

by Paolo Trucillo and Ernesto Di Maio

Polymers 2021, 13(10), 1608; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13101608 - 16 May 2021

Cited by 11 | Viewed by 6560

Abstract

This work represents an overview on types of wounds according to their definition, classification and dressing treatments. Natural and synthetic polymeric wound dressings types have been analyzed, providing a historical overview, from ancient to modern times. Currently, there is a wide choice of materials for the treatment of wounds, such as hydrocolloids, polyurethane and alginate patches, wafers, hydrogels and semi-permeable film dressings. These systems are often loaded with drugs such as antibiotics for the simultaneous delivery of drugs to prevent or cure infections caused by the exposition of blood vessel to open air. Among the presented techniques, a focus on foams has been provided, describing the most diffused branded products and their chemical, physical, biological and mechanical properties. Conventional and high-pressure methods for the production of foams for wound dressing are also analyzed in this work, with a proposed comparison in terms of process steps, efficiency and removal of solvent residue. Case studies, in vivo tests and models have been reported to identify the real applications of the produced foams. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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38 pages, 3626 KiB

Open AccessReview

Nanocellulose in Drug Delivery and Antimicrobially Active Materials

by Kaja Kupnik, Mateja Primožič, Vanja Kokol and Maja Leitgeb

Polymers 2020, 12(12), 2825; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12122825 - 27 Nov 2020

Cited by 63 | Viewed by 6647

Abstract

In recent years, nanocellulose (NC) has also attracted a great deal of attention in drug delivery systems due to its unique physical properties, specific surface area, low risk of cytotoxicity, and excellent biological properties. This review is focused on nanocellulose based systems acting as carriers to be used in drug or antimicrobial delivery by providing different but controlled and sustained release of drugs or antimicrobial agents, respectively, thus showing potential for different routes of applications and administration. Microorganisms are increasingly resistant to antibiotics, and because, generally, the used metal or metal oxide nanoparticles at some concentration have toxic effects, more research has focused on finding biocompatible antimicrobial agents that have been obtained from natural sources. Our review contains the latest research from the last five years that tested nanocellulose-based materials in the field of drug delivery and antimicrobial activity. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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31 pages, 6528 KiB

Open AccessReview

Microbial Exopolysaccharides as Drug Carriers

by Antonio Tabernero and Stefano Cardea

Polymers 2020, 12(9), 2142; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12092142 - 19 Sep 2020

Cited by 21 | Viewed by 4700

Abstract

Microbial exopolysaccharides are peculiar polymers that are produced by living organisms and protect them against environmental factors. These polymers are industrially recovered from the medium culture after performing a fermentative process. These materials are biocompatible and biodegradable, possessing specific and beneficial properties for biomedical drug delivery systems. They can have antitumor activity, they can produce hydrogels with different characteristics due to their molecular structure and functional groups, and they can even produce nanoparticles via a self-assembly phenomenon. This review studies the potential use of exopolysaccharides as carriers for drug delivery systems, covering their versatility and their vast possibilities to produce particles, fibers, scaffolds, hydrogels, and aerogels with different strategies and methodologies. Moreover, the main properties of exopolysaccharides are explained, providing information to achieve an adequate carrier selection depending on the final application. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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29 pages, 1587 KiB

Open AccessReview

The Use of Poly(N-vinyl pyrrolidone) in the Delivery of Drugs: A Review

by Paola Franco and Iolanda De Marco

Polymers 2020, 12(5), 1114; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12051114 - 13 May 2020

Cited by 166 | Viewed by 12874

Abstract

Polyvinylpyrrolidone (PVP) is a hydrophilic polymer widely employed as a carrier in the pharmaceutical, biomedical, and nutraceutical fields. Up to now, several PVP-based systems have been developed to deliver different active principles, of both natural and synthetic origin. Various formulations and morphologies have been proposed using PVP, including microparticles and nanoparticles, fibers, hydrogels, tablets, and films. Its versatility and peculiar properties make PVP one of the most suitable and promising polymers for the development of new pharmaceutical forms. This review highlights the role of PVP in drug delivery, focusing on the different morphologies proposed for different polymer/active compound formulations. It also provides detailed information on active principles and used technologies, optimized process parameters, advantages, disadvantages, and final applications. Full article

(This article belongs to the Special Issue Polymers and Drug Delivery Systems)

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