Polymeric Materials for Drug Delivery Application

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Biomacromolecules, Biobased and Biodegradable Polymers".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 32811

Special Issue Editors

Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: polymer chemistry; synthesis and modification of polymers; drug delivery systems
Special Issues, Collections and Topics in MDPI journals
Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR 54124 Thessaloniki, Greece
Interests: synthesis and characterization of polyesters; development of biobased polymers; biodegradable polymers; polymer composites and nanocomposites; synthesis and characterization of copolymers; polymer blends; recycling of polymers with various techniques; enzymatic hydrolysis studies; modification of natural polymers; polymer for wastewater treatment pollutant removal; polymers for tissue engineering and drug delivery applications; drug–polymer solid dispersions; drug targeting; drug nanoencapsulation and microencapsulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Drug delivery systems are one of the main issues of interest for the scientific community. Polymers are directly related with these systems, since they are extensively used in their formulations either as excipients, used to increase the solubility of the drugs, control their release or stabilize their solutions, or as polymeric matrices, i.e., macro/nanoparticles, matrices for melt mixing procedures. Natural polymers, such as chitosan, carrageenan, cellulose, starch, hyaluronic acid, alginic acid, and their modified analogs, or synthetic polymers, such as poly(N-vinyl-2-pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), polyacrylates, poly(lactic acid) (PLA), poly(glycolic acid (PGA) and their PLGA copolymers, poly(ortho esters), polycaprolactone (PCL), polyanhydrides, polyphosphazenes, Poloxamer, Soluplus, etc., have been used and extensively studied in drug delivery systems. Today, it is recognized that polymers are of high importance in the pharmaceutical field due to their advantages: the ability to deliver either hydrophilic or hydrophobic drugs, the convenience of getting administered through different pathways to patients (oral, nasal, by inhalation, parenteral), and the maintenance of the therapeutic concentration of drugs (shorter half-life) in plasma for longer periods of time by controlling their release. However, in order to be used as drug delivery systems, polymers should possess the following requirements: drug vehicles should be bio-degradable, biocompatible, nontoxic, non-immunogenic, physically and chemically stable in vivo and in vitro conditions, and readily eliminated from the body without any problems (low accumulation in organs).

The present Special Issue aims at covering all the aspects of innovative polymeric drug delivery systems. Special emphasis will be given to novel polymeric matrices used for this objective without excluding already studied polymers, copolymers, and blends with novel formulations and applications. We also intend to include in this Special Issue, apart from classic techniques, liposomes, dendrimers, composites, macro- or prodrugs, thermosensitive and pH sensitive polymers, electrospinning prepared matrices, melt mixing, solid dispersions, hydrogels, spray and freeze drying, etc., novel techniques such as 3D printing, contact lenses, microneedles, long acting injectables (LAI) or others used for drug delivery applications. During the past few decades, there has been an increasing interest in the development of polymeric biodegradable micro/nanoparticles for effective drug, peptide, protein, and DNA delivery. Incorporation of the drug into a particulate nanocarrier can protect the active substance from in vivo and in vitro degradation. Such drug delivery nanosystems constitute a significant section or part of nanomedicine. It also offers possibilities such as targeting, improving therapeutic effect, prolonging biological activity, controlling drug release rate and decreasing the frequency of administration, in other words delivering a certain amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body (ideal drug loading). All these issues will be included in the suggested Special Issue.

In vivo experiments concerning innovative polymeric drug delivery systems will also be accepted.

Dr. Stavroula Nanaki
Prof. Dimitrios Bikiaris
Guest Editors

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Keywords

  • polymer synthesis
  • modification of polymers
  • drug delivery systems

Published Papers (7 papers)

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Research

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10 pages, 1412 KiB  
Article
Crosslinking-Dependent Drug Kinetics in Hydrogels for Ophthalmic Delivery
by Nicole Mortensen, Parker Toews and Jeffrey Bates
Polymers 2022, 14(2), 248; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14020248 - 08 Jan 2022
Cited by 2 | Viewed by 1324
Abstract
Drug-diffusion kinetics in 2-hydroxyethyl methacrylate hydrogels were studied as a function of the crosslinking density and porosity. By varying the concentration of the crosslinker, tetraethylene glycol dimethacrylate, we demonstrated how the release of Timolol maleate could be optimized to allow for efficient drug [...] Read more.
Drug-diffusion kinetics in 2-hydroxyethyl methacrylate hydrogels were studied as a function of the crosslinking density and porosity. By varying the concentration of the crosslinker, tetraethylene glycol dimethacrylate, we demonstrated how the release of Timolol maleate could be optimized to allow for efficient drug delivery. FTIR and spectrophotometry supplied optical inferences into the functional groups present. By studying the swelling and degradation of hydrogels, supplemented with drug-release kinetics studies, the relationship between these two tenets could be formulated. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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22 pages, 25652 KiB  
Article
Modified Biochanin A Release from Dual pH- and Thermo-Responsive Copolymer Hydrogels
by Ivana Gajić, Snežana Ilić-Stojanović, Ana Dinić, Aleksandar Zdravković, Ljiljana Stanojević, Vesna Nikolić and Ljubiša Nikolić
Polymers 2021, 13(3), 426; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13030426 - 29 Jan 2021
Cited by 8 | Viewed by 2278
Abstract
The temperature- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid), p(NIPAM-co-AA), copolymer was synthesized by free radical polymerization and examined as a carrier for modified release of biochanin A. Biochanin A is a biologically active methoxylated isoflavone which exhibits estrogenic and other pharmacological activities. Due [...] Read more.
The temperature- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid), p(NIPAM-co-AA), copolymer was synthesized by free radical polymerization and examined as a carrier for modified release of biochanin A. Biochanin A is a biologically active methoxylated isoflavone which exhibits estrogenic and other pharmacological activities. Due to its poor aqueous solubility and extensive first-pass metabolism, biochanin A has low bioavailability. The aim of this work was to incorporate biochanin A into the synthesized p(NIPAM-co-AA) copolymer and to examine its release at the body temperature and pH values that correspond to pH values of vaginal and rectal cavities. The amount of released biochanin A was monitored by the ultra-visible spectroscopy (UV-Vis) method. The structure of synthesized p(NIPAM-co-AA) copolymer and copolymer with incorporated biochanin A were characterized by using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) methods. The content of residual monomers in the synthesized copolymer was analyzed by using the high-pressure liquid chromatography (HPLC) method. The swelling behavior of p(NIPAM-co-AA) copolymer was monitored in relation to the temperature and pH values of the surrounding medium. For modelling the process of p(NIPAM-co-AA) copolymer swelling, the full three-level factorial design was applied. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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20 pages, 3690 KiB  
Article
Synthesis and Cytotoxicity Study of Magnetite Nanoparticles Coated with Polyethylene Glycol and Sorafenib–Zinc/Aluminium Layered Double Hydroxide
by Mona Ebadi, Kalaivani Buskaran, Saifullah Bullo, Mohd Zobir Hussein, Sharida Fakurazi and Giorgia Pastorin
Polymers 2020, 12(11), 2716; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12112716 - 17 Nov 2020
Cited by 14 | Viewed by 3061
Abstract
In the last two decades, the development of novel approaches for cancer treatment has attracted intense attention due to the growing number of patients and the inefficiency of the available current conventional treatments. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized [...] Read more.
In the last two decades, the development of novel approaches for cancer treatment has attracted intense attention due to the growing number of patients and the inefficiency of the available current conventional treatments. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the co-precipitation method in an alkaline medium. Then the nanoparticles were chemically modified by coating them with polyethylene glycol (PEG) and sorafenib (SO)–zinc/aluminum layered double hydroxide (ZLDH) to improve their biocompatibility. The SPIONs and their coated and drug-loaded nanoparticles, M-PEG–SO–ZLDH are of the crystalline phase with the presence of C, O, Al, Fe, Cl, Zn in the latter, indicating the presence of the coating layers on the surface of the SPIONs. The superparamagnetic properties of the bare SPIONs were found to be reduced but retained in its coated drug delivery nanoparticles, M-PEG–SO–ZLDH. The latter has an average particle size of 16 nm and the release of the drug from it was found to be governed by the pseudo-second-order kinetic. The cytotoxicity and biocompatibility evaluation of the drug-loaded magnetic nanoparticles using 3T3 and HepG2 cells using the diphenyltetrazolium bromide (MTT) assays shows that the synthesized nanoparticles were less toxic than the pure drug. This preliminary study indicates that the prepared nanoparticles are suitable to be used for the drug delivery system. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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21 pages, 5882 KiB  
Article
Systematic Studies on Surface Erosion of Photocrosslinked Polyanhydride Tablets and Data Correlation with Release Kinetic Models
by Armin Geraili and Kibret Mequanint
Polymers 2020, 12(5), 1105; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12051105 - 12 May 2020
Cited by 21 | Viewed by 4699
Abstract
Photocrosslinkable polyanhydrides that undergo surface erosion are suitable materials for controlled-release drug delivery systems. Investigating the impact of different parameters on their erosion behavior is essential before use in drug delivery systems. Although their synthesis is well-established, parameters that may substantially affect the [...] Read more.
Photocrosslinkable polyanhydrides that undergo surface erosion are suitable materials for controlled-release drug delivery systems. Investigating the impact of different parameters on their erosion behavior is essential before use in drug delivery systems. Although their synthesis is well-established, parameters that may substantially affect the erosion of thiol-ene polyanhydrides including temperature and pH of the media, the geometry of the polymers, and the media shaking rate (the convective force for the polymer erosion), have not yet been studied. This study explores the effects of different environmental and geometric parameters on mass loss (erosion) profiles of polyanhydrides synthesized by thiol-ene photopolymerization. A comparative study on several release kinetic models fitting is also described for a better understanding of the polymer erosion behavior. The results demonstrated that although the temperature was the only parameter that affected the induction period substantially, the mass-loss rate was influenced by the polymer composition, tablet geometry, temperature, pH, and mass transfer (shaking) rate. With regard to geometrical parameters, polymers with the same surface area to volume ratios showed similar mass loss trends despite their various volumes and surface areas. The mass loss of polyanhydride tablets with more complicated geometries than a simple slab was shown to be non-linear, and the kinetic model study indicated the dominant surface erosion mechanism. The results of this study allow for designing and manufacturing efficient delivery systems with a high-predictable drug release required in precision medicine using surface-erodible polyanhydrides. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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22 pages, 4031 KiB  
Article
Effect of Poly(vinyl alcohol) on Nanoencapsulation of Budesonide in Chitosan Nanoparticles via Ionic Gelation and Its Improved Bioavailability
by Georgia Michailidou, Nina Maria Ainali, Eleftheria Xanthopoulou, Stavroula Nanaki, Margaritis Kostoglou, Emmanuel N. Koukaras and Dimitrios N. Bikiaris
Polymers 2020, 12(5), 1101; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12051101 - 12 May 2020
Cited by 33 | Viewed by 3260
Abstract
Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification [...] Read more.
Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification of it, using also poly(vinyl alcohol) (PVA) as a surfactant. Scanning electron microscopy (SEM) micrographs revealed that spherical nanoparticles were successfully prepared with average sizes range between 363 and 543 nm, as were measured by dynamic light scattering (DLS), while zeta potential verified their positive charged surface. X-ray diffraction (XRD) patterns revealed that BUD was encapsulated in crystalline state in nanoparticles but with a lower degree of crystallinity than the neat drug, which was also proven by differential scanning calorimetry (DSC) and melting peak measurements. This could be attributed to interactions that take place between BUD and CS, which were revealed by FTIR and by an extended computational study. An in vitro release study of budesonide showed a slight enhancement in the BUD dissolution profile, compared to the neat drug. However, drug release was substantially increased by introducing PVA during the nanoencapsulation procedure, which is attributed to the higher amorphization of BUD on these nanoparticles. The release curves were analyzed using a diffusion model that allows estimation of BUD diffusivity in the nanoparticles. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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24 pages, 6219 KiB  
Article
New Biodegradable Poly(l-lactide)-Block-Poly(propylene adipate) Copolymer Microparticles for Long-Acting Injectables of Naltrexone Drug
by Stavroula Nanaki, Athina Viziridou, Alexandra Zamboulis, Margaritis Kostoglou, Georgios Z. Papageorgiou and Dimitrios N. Bikiaris
Polymers 2020, 12(4), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12040852 - 07 Apr 2020
Cited by 14 | Viewed by 3350
Abstract
In the present study, novel block copolymers of poly(l-lactide)-block-poly(propylene adipate) (PLLA-b-PPAd) were synthesized in two ratios, 90/10 and 75/25 w/w and were further investigated as long-acting injectable (LAI) polymeric matrices in naltrexone base microparticle formulations. The synthesized [...] Read more.
In the present study, novel block copolymers of poly(l-lactide)-block-poly(propylene adipate) (PLLA-b-PPAd) were synthesized in two ratios, 90/10 and 75/25 w/w and were further investigated as long-acting injectable (LAI) polymeric matrices in naltrexone base microparticle formulations. The synthesized polymers were characterized by 1H-NMR, 13C-NMR, FTIR, XRD, TGA and DSC. NMR and FTIR spectroscopies confirmed the successful synthesis of copolymers while DSC showed that these are block copolymers with well-defined and separated blocks. Microparticles were prepared by single emulsification method and were further characterized. Nanoparticles in the range of 0.4–4.5 μm were prepared as indicated by SEM, with copolymers giving the lowest particle size. By XRD and DSC it was found that naltrexone was present in the amorphous state in its microparticles. Dissolution study showed a drug release extending over seven days, indicating that these novel PLLA-b-PPAd copolymers could be promising matrices for naltrexone’s LAI formulations. It was evidenced that drug release depended on the copolymer composition. Model release studies showed that drug release is controlled by diffusion. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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Review

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45 pages, 3261 KiB  
Review
Stimuli-Responsive Polymeric Nanocarriers for Drug Delivery, Imaging, and Theragnosis
by Sabya Sachi Das, Priyanshu Bharadwaj, Muhammad Bilal, Mahmood Barani, Abbas Rahdar, Pablo Taboada, Simona Bungau and George Z. Kyzas
Polymers 2020, 12(6), 1397; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12061397 - 22 Jun 2020
Cited by 271 | Viewed by 13603
Abstract
In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers [...] Read more.
In the past few decades, polymeric nanocarriers have been recognized as promising tools and have gained attention from researchers for their potential to efficiently deliver bioactive compounds, including drugs, proteins, genes, nucleic acids, etc., in pharmaceutical and biomedical applications. Remarkably, these polymeric nanocarriers could be further modified as stimuli-responsive systems based on the mechanism of triggered release, i.e., response to a specific stimulus, either endogenous (pH, enzymes, temperature, redox values, hypoxia, glucose levels) or exogenous (light, magnetism, ultrasound, electrical pulses) for the effective biodistribution and controlled release of drugs or genes at specific sites. Various nanoparticles (NPs) have been functionalized and used as templates for imaging systems in the form of metallic NPs, dendrimers, polymeric NPs, quantum dots, and liposomes. The use of polymeric nanocarriers for imaging and to deliver active compounds has attracted considerable interest in various cancer therapy fields. So-called smart nanopolymer systems are built to respond to certain stimuli such as temperature, pH, light intensity and wavelength, and electrical, magnetic and ultrasonic fields. Many imaging techniques have been explored including optical imaging, magnetic resonance imaging (MRI), nuclear imaging, ultrasound, photoacoustic imaging (PAI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). This review reports on the most recent developments in imaging methods by analyzing examples of smart nanopolymers that can be imaged using one or more imaging techniques. Unique features, including nontoxicity, water solubility, biocompatibility, and the presence of multiple functional groups, designate polymeric nanocues as attractive nanomedicine candidates. In this context, we summarize various classes of multifunctional, polymeric, nano-sized formulations such as liposomes, micelles, nanogels, and dendrimers. Full article
(This article belongs to the Special Issue Polymeric Materials for Drug Delivery Application)
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