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Engineering and Material Advances in Polymer-Based 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 (30 April 2019) | Viewed by 57886

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Special Issue Editors

Prof. Dr. Zeeshan Ahmad

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Guest Editor

Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK
Interests: nanotechnology; pharmaceutical engineering; fibers; nanoparticles; manufacturing; biomaterials; dosage forms
Special Issues, Collections and Topics in MDPI journals

Dr. Ming-Wei Chang

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Guest Editor

Nanotechnology and Integrated Bioengineering Centre, University of Ulster, Jordanstown Campus, Newtownabbey BT37 0QB, Northern Ireland, UK
Interests: biomaterials; drug delivery; sensors; 3D printing; nanotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in pharmaceutical dosage form design have been diverse; benefiting from advances in materials (e.g., smart, responsive, biocompatible), material design (e.g., size, shape, application driven in vitro and in vivo properties) and material engineering (e.g., processes and optimisation) aspects. Outside of the active pharmaceutical ingredient (API), polymeric excipients are crucial in advancing the development of new drug delivery systems which in turn enable better delivery of biological and active molecules through targeting, improved biocompatibility, sustained and controlled delivery and even economic benefits. This Special Issue will focus on polymer based drug delivery systems, providing the readership with timely research and review articles detailing various aspects of macromolecules from their design, use, engineering and end applications.

Prof. Zeeshan Ahmad
Prof. Ming-Wei Chang
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

Polymers
Excipients
Polymer engineering
Nanotechnology
Micromete
Coatings
Prticles
Targeting
Controlled release
Biocompatibility
Dosage form design
Pharmaceutics
Drug delivery
Optimisation

Published Papers (11 papers)

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Research

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13 pages, 3834 KiB

Open AccessArticle

High Efficiency Fabrication of Chitosan Composite Nanofibers with Uniform Morphology via Centrifugal Spinning

by Zhen Li, Shunqi Mei, Yajie Dong, Fenghua She and Lingxue Kong

Polymers 2019, 11(10), 1550; https://doi.org/10.3390/polym11101550 - 24 Sep 2019

Cited by 51 | Viewed by 4533

Abstract

While electrospinning has been widely employed to spin nanofibers, its low production rate has limited its potential for industrial applications. Comparing with electrospinning, centrifugal spinning technology is a prospective method to fabricate nanofibers with high productivity. In the current study, key parameters of the centrifugal spinning system, including concentration, rotational speed, nozzle diameter and nozzle length, were studied to control fiber diameter. An empirical model was established to determine the final diameters of nanofibers via controlling various parameters of the centrifugal spinning process. The empirical model was validated via fabrication of carboxylated chitosan (CCS) and polyethylene oxide (PEO) composite nanofibers. DSC and TGA illustrated that the thermal properties of CCS/PEO nanofibers were stable, while FTIR-ATR indicated that the chemical structures of CCS and PEO were unchanged during composite fabrication. The empirical model could provide an insight into the fabrication of nanofibers with desired uniform diameters as potential biomedical materials. This study demonstrated that centrifugal spinning could be an alternative method for the fabrication of uniform nanofibers with high yield. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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15 pages, 4952 KiB

Open AccessArticle

T-Shaped Microfluidic Junction Processing of Porous Alginate-Based Films and Their Characteristics

by Betul Mutlu, Muhammad Farhan and Israfil Kucuk

Polymers 2019, 11(9), 1386; https://doi.org/10.3390/polym11091386 - 23 Aug 2019

Cited by 10 | Viewed by 3918

Abstract

In this work, highly monodisperse porous alginate films from bubble bursting were formed on a glass substrate at ambient temperature, by a T-shaped microfluidic junction device method using polyethylene glycol (PEG) stearate and phospholipid as precursors in some cases. Various polymer solution concentrations and feeding liquid flow rates were applied for the generation of monodisperse microbubbles, followed by the conversion of the bubbles to porous film structures on glass substrates. In order to compare the physical properties of polymeric solutions, the effects of alginate, PEG stearate (surfactant), and phospholipid concentrations on the flowability of the liquid in a T-shaped microfluidic junction device were studied. To tailor microbubble diameter and size distribution, a method for controlling the thinning process of the bubbles’ shell was also explored. In order to control pore size, shape, and surface as well as internal structure morphologies in the scalable forming of alginate polymeric films, the effect of the feeding liquid’s flow rate and concentrations of PEG-stearate and phospholipid was also studied. Digital microscopy images revealed that the as-formed alginate films at the flow rate of 100 µL·min⁻¹ and the N₂ gas pressure of 0.8 bar have highly monodisperse microbubbles with a polydispersity index (PDI) of approximately 6.5%. SEM captures also revealed that the as-formed alginate films with high PDI value have similar monodisperse porous surface and internal structure morphologies, with the exception that the as-formed alginate films with the help of phospholipids were mainly formed under our experimental environment. From the Fourier-transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) measurements, we concluded that no chemical composition changes, thermal influence, and crystal structural modifications were observed due to the T-shaped microfluidic junction device technique. The method used in this work could expand and enhance the use of alginate porous films in a wide range of bioengineering applications, especially in tissue engineering and drug delivery, such as studying release behaviors to different internal and surface morphologies. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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18 pages, 4766 KiB

Open AccessArticle

Plasticiser-Free 3D Printed Hydrophilic Matrices: Quantitative 3D Surface Texture, Mechanical, Swelling, Erosion, Drug Release and Pharmacokinetic Studies

by Zara Khizer, Muhammad R. Akram, Rai M. Sarfraz, Jorabar Singh Nirwan, Samia Farhaj, Maria Yousaf, Tariq Hussain, Shan Lou, Peter Timmins, Barbara R. Conway and Muhammad Usman Ghori

Polymers 2019, 11(7), 1095; https://doi.org/10.3390/polym11071095 - 28 Jun 2019

Cited by 21 | Viewed by 5511

Abstract

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95–105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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23 pages, 5509 KiB

Open AccessArticle

Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects

by Marina V. Novoselova, Sergey V. German, Olga A. Sindeeva, Oleg A. Kulikov, Olga V. Minaeva, Ekaterina P. Brodovskaya, Valentin P. Ageev, Mikhail N. Zharkov, Nikolay A. Pyataev, Gleb B. Sukhorukov and Dmitry A. Gorin

Polymers 2019, 11(6), 1082; https://doi.org/10.3390/polym11061082 - 25 Jun 2019

Cited by 24 | Viewed by 4198

Abstract

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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16 pages, 3662 KiB

Open AccessArticle

A Hypericin Delivery System Based on Polydopamine Coated Cerium Oxide Nanorods for Targeted Photodynamic Therapy

by Yang Wang, Yu Zhang, Ming Jin, Yinghua Lv, Zhichao Pei and Yuxin Pei

Polymers 2019, 11(6), 1025; https://doi.org/10.3390/polym11061025 - 10 Jun 2019

Cited by 13 | Viewed by 3201

Abstract

Photodynamic therapy (PDT) as a non-aggressive therapy with fewer side effects has unique advantages over traditional treatments. However, PDT still has certain limitations in clinical applications, mainly because most photosensitizers utilized in PDT are hydrophobic compounds, which will self-aggregate in the aqueous phase and cause undesirable effects. In order to resolve this, we utilized the self-polymerization of dopamine molecules under alkaline conditions to coat cerium oxide nanorods (CeONR) with a dense polydopamine (PDA) film. Thereafter, thiolated galactose (Gal-SH) and hypericin (Hyp) were modified and loaded onto the surface to construct CeONR@PDA-Gal/Hyp, respectively, which can be used for targeted photodynamic therapy of human hepatoma HepG2 cells. CeONR@PDA-Gal/Hyp was characterized by transmission electron microscope (TEM), Zeta potential, Ultraviolet-visible (UV-Vis), and fluorescence spectroscopy, respectively. This hypericin delivery system possesses good biocompatibility and specific targeting ability, where the galactose units on the surface of CeONR@PDA-Gal/Hyp can specifically recognize the asialo-glycoprotein receptors (ASGP-R), which overexpress on HepG2 cell membrane. Furthermore, Hyp will detach from the surface of CeONR@PDA-Gal/Hyp after the nanorods enter cancer cells, and shows excellent PDT effect under the irradiation of light with a wavelength of 590 nm. Our work exemplifies a novel targeted delivery of hydrophobic photosensitizers for cancer treatment. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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15 pages, 7195 KiB

Open AccessEditor’s ChoiceArticle

Essential Oils-Loaded Polymer Particles: Preparation, Characterization and Antimicrobial Property

by Francesca Froiio, Lorianne Ginot, Donatella Paolino, Noureddine Lebaz, Abderrazzak Bentaher, Hatem Fessi and Abdelhamid Elaissari

Polymers 2019, 11(6), 1017; https://doi.org/10.3390/polym11061017 - 09 Jun 2019

Cited by 52 | Viewed by 6959

Abstract

In the last few years, essential oils (EOs) derived from plants have aroused great interest due to their well-known antimicrobial activity. Unfortunately, they present several limitations in their use, such as photosensitivity, temperature sensitivity, high volatility, and poor water solubility. The encapsulation technique represents a good solution to these problems and ensures protection of the functional properties of essential oils. In this work, bergamot essential oil (BEO) and sweet orange essential oil (OEO) loaded-Eudragit^® RS 100 (EuRS100) nanoparticles (NPs) were prepared by using the nanoprecipitation technique. We obtained nanoparticles characterized by a mean diameter of 57 to 208 nm and a positive surface charge (39 to 74 mV). The antibacterial activity of the obtained systems against Escherichia coli was in vitro investigated. We demonstrated that both orange and bergamot essential oils were successfully encapsulated and our nanoparticles have good antibacterial activity. Finally, in order to evaluate the potential applicability of OEONps to prolong fresh orange juice shelf-life, survival of E. coli during a storage period of one week at 25 °C was investigated: Orange essential oil-loaded nanoparticles (OEONPs) have been able to prolong the orange juice shelf life. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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17 pages, 1360 KiB

Open AccessArticle

Osmoprotectants in Hybrid Liposome/HPMC Systems as Potential Glaucoma Treatment

by Miguel Gómez-Ballesteros, José Javier López-Cano, Irene Bravo-Osuna, Rocío Herrero-Vanrell and Irene Teresa Molina-Martínez

Polymers 2019, 11(6), 929; https://doi.org/10.3390/polym11060929 - 28 May 2019

Cited by 23 | Viewed by 3356

Abstract

The combination of acetazolamide-loaded nano-liposomes and Hydroxypropyl methylcellulose (HPMC) with similar components to the preocular tear film in an osmoprotectant media (trehalose and erythritol) is proposed as a novel strategy to increase the ocular bioavailability of poorly soluble drugs. Ophthalmic formulations based on acetazolamide-loaded liposomes, dispersed in the osmoprotectant solution (ACZ-LP) or in combination with HPMC (ACZ-LP-P) were characterized and in vivo evaluated. The pH and tonicity of both formulations resulted in physiological ranges. The inclusion of HPMC produced an increment in viscosity (from 0.9 to 4.7 mPa·s. 64.9 ± 2.6% of acetazolamide initially included in the formulation was retained in vesicles. In both formulations, a similar onset time (1 h) and effective time periods were observed (7 h) after a single instillation (25 μL) in normotensive rabbits’ eyes. The AUC_0–8h of the ACZ-LP-P was 1.5-fold higher than of ACZ-LP (p < 0.001) and the maximum hypotensive effect resulted in 1.4-fold higher (p < 0.001). In addition, the formulation of ACZ in the hybrid liposome/HPMC system produced a 30.25-folds total increment in ocular bioavailability, compared with the drug solution. Excellent tolerance in rabbits’ eyes was confirmed during the study. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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17 pages, 3797 KiB

Open AccessArticle

Amylase-Sensitive Polymeric Nanoparticles Based on Dextran Sulfate and Doxorubicin with Anticoagulant Activity

by Nikolay A. Pyataev, Pavel S. Petrov, Olga V. Minaeva, Mikhail N. Zharkov, Oleg A. Kulikov, Axeksandr V. Kokorev, Ekaterina P. Brodovskaya, Ivan A. Yurlov, Ilya V. Syusin, Andrey V. Zaborovskiy and Larisa A. Balykova

Polymers 2019, 11(5), 921; https://doi.org/10.3390/polym11050921 - 25 May 2019

Cited by 6 | Viewed by 2946

Abstract

This study looked into the synthesis and study of Dextrane Sulfate–Doxorubicin Nanoparticles (DS–Dox NP) that are sensitive to amylase and show anticoagulant properties. The particles were obtained by the method of solvent replacement. They had a size of 305 ± 58 nm, with a mass ratio of DS:Dox = 3.3:1. On heating to 37 °C, the release of Dox from the particles was equal to 24.2% of the drug contained. In the presence of amylase, this ratio had increased to 42.1%. The study of the biological activity of the particles included an assessment of the cytotoxicity and the effect on hemostasis and antitumor activity. In a study of cytotoxicity on the L929 cell culture, it was found that the synthesized particles had less toxicity, compared to free doxorubicin. However, in the presence of amylase, their cytotoxicity was higher than the traditional forms of the drug. In a study of the effect of DS–Dox NP on hemostasis, it was found that the particles had a heparin-like anticoagulant effect. Antitumor activity was studied on the model of ascitic Zaidel hepatoma in rats. The frequency of complete cure in animals treated with the DS–Dox nanoparticles was higher, compared to animals receiving the traditional form of the drug. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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12 pages, 2467 KiB

Open AccessArticle

Enhanced Transfection of Human Mesenchymal Stem Cells Using a Hyaluronic Acid/Calcium Phosphate Hybrid Gene Delivery System

by Jung Eun Lee, Yue Yin, Su Yeon Lim, E. Seul Kim, Jaeback Jung, Dahwun Kim, Ji Won Park, Min Sang Lee and Ji Hoon Jeong

Polymers 2019, 11(5), 798; https://doi.org/10.3390/polym11050798 - 04 May 2019

Cited by 27 | Viewed by 4898

Abstract

Human mesenchymal stem cells (hMSCs) show enormous potential in regenerative medicine and tissue engineering. However, current use of hMSCs in clinics is still limited because there is no appropriate way to control their behavior in vivo, such as differentiation to a desired cell type. Genetic modification may provide an opportunity to control the cells in an active manner. One of the major hurdles for genetic manipulation of hMSCs is the lack of an efficient and safe gene delivery system. Herein, biocompatible calcium phosphate (CaP)-based nanoparticles stabilized with a catechol-derivatized hyaluronic acid (dopa-HA) conjugate were used as a carrier for gene transfection to hMSCs for improved differentiation. Owing to the specific interactions between HA and CD44 of bone marrow-derived hMSCs, dopa-HA/CaP showed significantly higher transfection in hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxicity. The co-delivery of a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and micro RNA 148b (miRNA-148b) by dopa-HA/CaP achieved significantly improved osteogenic differentiation of hMSCs. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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Review

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27 pages, 3234 KiB

Open AccessReview

Polymer-Based Nanoparticle Strategies for Insulin Delivery

by Shazia Mansoor, Pierre P. D. Kondiah, Yahya E. Choonara and Viness Pillay

Polymers 2019, 11(9), 1380; https://doi.org/10.3390/polym11091380 - 22 Aug 2019

Cited by 74 | Viewed by 9462

Abstract

Diabetes mellitus (DM) is a chronic metabolic illness estimated to have affected 451 million individuals to date, with this number expected to significantly rise in the coming years. There are two main classes of this disease, namely type 1 diabetes (T1D) and type 2 diabetes (T2D). Insulin therapy is pivotal in the management of diabetes, with diabetic individuals taking multiple daily insulin injections. However, the mode of administration has numerous drawbacks, resulting in poor patient compliance. In order to optimize insulin therapy, novel drug delivery systems (DDSes) have been suggested, and alternative routes of administration have been investigated. A novel aspect in the field of drug delivery was brought about by the coalescence of polymeric science and nanotechnology. In addition to polymeric nanoparticles (PNPs), insulin DDSes can incorporate the use of nanoplatforms/carriers. A combination of these systems can bring about novel formulations and lead to significant improvements in the drug delivery system (DDS) with regard to therapeutic efficacy, bioavailability, increased half-life, improved transport through physical and chemical barriers, and controlled drug delivery. This review will discuss how recent developments in polymer chemistry and nanotechnology have been employed in a multitude of platforms as well as in administration routes for the safe and efficient delivery of insulin for the treatment of DM. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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24 pages, 3070 KiB

Open AccessReview

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery

by Courtney Lynch, Pierre P. D. Kondiah, Yahya E. Choonara, Lisa C. du Toit, Naseer Ally and Viness Pillay

Polymers 2019, 11(8), 1371; https://doi.org/10.3390/polym11081371 - 20 Aug 2019

Cited by 57 | Viewed by 7953

Abstract

The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye. Full article

(This article belongs to the Special Issue Engineering and Material Advances in Polymer-Based Drug Delivery Systems)

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