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Polymeric Biomaterials 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 (15 February 2022) | Viewed by 38058

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Prof. Dr. Farid Bakir

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Guest Editor

Arts et Metiers Institute of Technology, CNAM, LIFSE, HESAM University, 75013 Paris, France
Interests: biopolymers; drug eluting stent; drug release mechanisms; cardiovascular diseases; kinetic models; polymer matrix; in-vitro assays
Special Issues, Collections and Topics in MDPI journals

Dr. Navideh Abbasnezhad

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Guest Editor

Arts et Metiers Institute of Technology, CNAM, LIFSE, HESAM University, 75013 Paris, France
Interests: polymeric biomaterials; drug eluting stent; drug release mechanisms; cardiovascular diseases; kinetic models; polymer matrix; in-vitro assays
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polymeric biomaterials are widely used in oral and targeted drug delivery systems, particularly in tablets and microcapsules, microparticles, microspheres, patches, balloons and drug eluting stents, related to different pathologies. Developing and designing a drug delivery system, corresponding to a specific therapy for achieving a desired release profile, maintaining a sufficient mechanical stress, and minimizing secondary effects, is of importance. Multiple advances have been made in using polymers in these regards, both in terms of their intrinsic properties and in their processing methods.

Evaluating these conjugated carriers by considering variations in the physical and mechanical properties of polymers, and the effects of different factors such as temperature, initial drug load, circulation rate, pH, etc., are among the subjects targeted here.

This Special Issue will cover, but is not limited to, all original reviews and research articles dedicated to:

The potential of polymers as drug carriers, in in vitro, ex vivo or in vivo release tests;
Physiochemical and mechanical characterization;
The influence of the manufacturing processes;
Design and optimization methods;
The analysis of release profiles by considering different release mechanisms;
Mathematical models and numerical simulation.

Prof. Dr. Farid Bakir
Dr. Navideh Abbasnezhad
Guest Editors

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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

polymeric biomaterials
drug delivery systems
physical and mechanical characterizations
drug release mechanisms and kinetics
numerical and empirical modeling
polymer processing and manufacturing
biodegradability
biocompatibility

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Published Papers (10 papers)

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21 pages, 6230 KiB

Open AccessArticle

Biological Safety Assessments of High-Purified Ovine Collagen Type I Biomatrix for Future Therapeutic Product: International Organisation for Standardisation (ISO) and Good Laboratory Practice (GLP) Settings

by Nur Izzah Md Fadilah, Nazeha Ahmat, Looi Qi Hao, Manira Maarof, Nor Fadilah Rajab, Ruszymah Binti Hj Idrus and Mh Busra Fauzi

Polymers 2023, 15(11), 2436; https://doi.org/10.3390/polym15112436 - 24 May 2023

Cited by 6 | Viewed by 2162

Abstract

Wound care management is incredibly challenging for chronic injuries, despite the availability of various types of wound care products in the market. However, most current wound-healing products do not attempt to mimic the extracellular matrix (ECM) and simply provide a barrier function or wound covering. Collagen is a natural polymer that involves a major constituent of the ECM protein, thus making it attractive to be used in skin tissue regeneration during wound healing. This study aimed to validate the biological safety assessments of ovine tendon collagen type-I (OTC-I) in the accredited laboratory under ISO and GLP settings. It is important to ensure that the biomatrix will not stimulate the immune system to produce any adverse reaction. Therefore, we successfully extracted collagen type-I from the ovine tendon (OTC- I) using a method of low-concentration acetic acid. The three-dimensional (3D) skin patch of spongy OTC-I was a soft and white colour, being tested for safety and biocompatibility evaluations based on ISO 10993-5, ISO 10993-10, ISO 10993-11, ISO 10993-23, USP 40 <151>, and OECD 471. For the dermal sensitisation and acute irritation test, none of the tested animals displayed any erythema or oedema effects (p > 0.005). In addition, there were no abnormalities detected in the organ of the mice after being exposed to OTC-I; additionally, no morbidity and mortality were observed in the acute systemic test under the guideline of ISO 10993-11:2017. The grade 0 (non-reactive) based on ISO 10993-5:2009 was graded for the OTC-I at 100% concentration and the mean number of the revertant colonies did not exceed 2-fold of the 0.9% w/v sodium chloride compared to the tester strains of S. typhimurium (TA100, TA1535, TA98, TA1537), and E. coli (WP2 trp uvrA). Our study revealed that OTC-I biomatrix does not present any adverse effects or abnormalities in the present study’s condition of induced skin sensitization effect, mutagenic and cytotoxic towards cells and animals. This biocompatibility assessment demonstrated a good agreement between in vitro and in vivo results regarding the absence of skin irritation and sensitization potential. Therefore, OTC-I biomatrix is a potential medical device candidate for future clinical trials focusing on wound care management. Full article

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

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16 pages, 2066 KiB

Open AccessArticle

Cytotoxicity, Colour Stability and Dimensional Accuracy of 3D Printing Resin with Three Different Photoinitiators

by Gi-Tae Kim, Hye-Bin Go, Jae-Hun Yu, Song-Yi Yang, Kwang-Mahn Kim, Sung-Hwan Choi and Jae-Sung Kwon

Polymers 2022, 14(5), 979; https://doi.org/10.3390/polym14050979 - 28 Feb 2022

Cited by 39 | Viewed by 6419

Abstract

Biocompatibility is important for the 3D printing of resins used in medical devices and can be affected by photoinitiators, one of the key additives used in the 3D printing process. The choice of ingredients must be considered, as the toxicity varies depending on the photoinitiator, and unreacted photoinitiator may leach out of the polymerized resin. In this study, the use of ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L) as a photoinitiator for the 3D printing of resin was considered for application in medical device production, where the cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical/physical properties were evaluated. Along with TPO-L, two conventional photoinitiators, phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide (BAPO) and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), were considered. A total of 0.1 mol% of each photoinitiator was mixed with the resin matrix to prepare a resin mixture for 3D printing. The specimens were printed using a direct light processing (DLP) type 3D printer. The 3D-printed specimens were postprocessed and evaluated for cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical properties in accordance with international standards and the methods described in previous studies. The TPO-L photoinitiator showed excellent biocompatibility and colour stability and possessed with an acceptable dimensional accuracy for use in the 3D printing of resins. Therefore, the TPO-L photoinitiator can be sufficiently used as a photoinitiator for dental 3D-printed resin. Full article

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

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11 pages, 994 KiB

Open AccessArticle

Release of Bisphenol A from Pit and Fissure Sealants According to Different pH Conditions

by Eun-Deok Jo, Sang-Bae Lee, Chung-Min Kang, Kwang-Mahn Kim and Jae-Sung Kwon

Polymers 2022, 14(1), 37; https://doi.org/10.3390/polym14010037 - 23 Dec 2021

Cited by 3 | Viewed by 2854

Abstract

Changes in intraoral pH can cause changes in the chemical decomposition and surface properties of treated resin-based pits and fissure sealants (sealant). The purpose of this study is to evaluate the release of bisphenol A (BPA) from sealants under three different pH conditions over time. The test specimen was applied with 6 sealants 5 mg each on a glass plate (10 × 10 mm) and photopolymerized. The samples were immersed for 10 min, 1 h, and 24 h in solutions of pH 3.0, 6.5, and 10.0 at 37 °C. BPA release was measured using a gas chromatography-mass spectrometer. A statistical analysis was performed by two-way ANOVA and one-way ANOVA to verify the effect of pH conditions and time on BPA release. The BPA concentration in the pH 3.0 group was higher at all points than with pH 6.5 and pH 10.0 (p < 0.05), and gradually increased over time (p < 0.05). As a result, it was confirmed that low pH negatively influences BPA release. Therefore, frequent exposure to low pH due to the consumption of various beverages after sealant treatment can negatively affect the sealant’s chemical stability in the oral cavity. Full article

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

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16 pages, 1724 KiB

Open AccessArticle

Design and Evaluation of Losartan Potassium Effervescent Floating Matrix Tablets: In Vivo X-ray Imaging and Pharmacokinetic Studies in Albino Rabbits

by Mohamed Rahamathulla, Srinivasan Saisivam, Abdullah Alshetaili, Umme Hani, Hosahalli Veerabhadrappa Gangadharappa, Sultan Alshehri, Mohammed M. Ghoneim and Faiyaz Shakeel

Polymers 2021, 13(20), 3476; https://doi.org/10.3390/polym13203476 - 10 Oct 2021

Cited by 17 | Viewed by 4041

Abstract

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug–polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit’s stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively. Full article

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

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13 pages, 1440 KiB

Open AccessArticle

Antioxidant Potential of the Bio-Based Fucose-Rich Polysaccharide FucoPol Supports Its Use in Oxidative Stress-Inducing Systems

by Bruno M. Guerreiro, Jorge Carvalho Silva, João Carlos Lima, Maria A. M. Reis and Filomena Freitas

Polymers 2021, 13(18), 3020; https://doi.org/10.3390/polym13183020 - 7 Sep 2021

Cited by 14 | Viewed by 3648

Abstract

Reactive oxygen species (ROS) are dangerous sources of macromolecular damage. While most derive from mitochondrial oxidative phosphorylation, their production can be triggered by exogenous stresses, surpassing the extinction capacity of intrinsic antioxidant defense systems of cells. Here, we report the antioxidant activity of FucoPol, a fucose-rich polyanionic polysaccharide produced by Enterobacter A47, containing ca. 17 wt% of negatively charged residues in its structure. Ferric reducing antioxidant power (FRAP) assays coupled to Hill binding kinetics fitting have shown FucoPol can neutralize ferricyanide and Fe³⁺-TPTZ species at an EC₅₀ of 896 and 602 µg/mL, respectively, with positive binding cooperativity (2.52 ≤ H ≤ 4.85). This reducing power is greater than most polysaccharides reported. Moreover, an optimal 0.25% w/v FucoPol concentration shown previously to be cryo- and photoprotective was also demonstrated to protect Vero cells against H₂O₂-induced acute exposure not only by attenuating metabolic viability decay, but also by accentuating post-stress proliferation capacity, whilst preserving cell morphology. These results on antioxidant activity provide evidence for the biopolymer’s ability to prevent positive feedback cascades of the radical-producing Fenton reaction. Ultimately, FucoPol provides a biotechnological alternative for implementation in cryopreservation, food supplementation, and photoprotective sunscreen formula design, as all fields benefit from an antioxidant functionality. Full article

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

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19 pages, 11016 KiB

Open AccessArticle

Monomer Conversion, Dimensional Stability, Biaxial Flexural Strength, Ion Release, and Cytotoxicity of Resin-Modified Glass Ionomer Cements Containing Methacrylate-Functionalized Polyacids and Spherical Pre-Reacted Glass Fillers

by Wisitsin Potiprapanpong, Whithipa Thepveera, Chutikarn Khamsuk, Somruethai Channasanon, Siriporn Tanodekaew, Somying Patntirapong, Naruporn Monmaturapoj and Piyaphong Panpisut

Polymers 2021, 13(16), 2742; https://doi.org/10.3390/polym13162742 - 16 Aug 2021

Cited by 12 | Viewed by 3087

Abstract

The aim of this study was to prepare RMGICs for pulp protection that contain polyacids functionalized with methacrylate groups (CMs) to enable light-activated polymerization without the need for toxic 2-hydroxyethyl methacrylate (HEMA) monomers. The effects of using CM liquids with 0 or 5 wt% HEMA on the physical/mechanical properties and cytotoxicity of the experimental RMGICs were assessed. Spherical pre-reacted glass fillers (SPG) were used as the powder phase. The experimental RMGICs were prepared by mixing SPG with CM liquid (0 wt% HEMA, F1) or CMH liquid (5 wt% HEMA, F2). Commercial materials (Vitrebond, VB; TheraCal LC, TC) were used for the comparisons. The degree of monomer conversion and fluoride release of both F1 and F2 were significantly lower than those of VB. F1 showed comparable biaxial flexural strength with VB but higher strength than TC. The dimensional stability (mass/volume changes) of the experimental materials was comparable with that of the commercial materials. F1 and F2 exhibited higher Sr/Ca ion release and relative cell viability than VB. The use of CMH liquid reduced the strength but enhanced the fluoride release of the experimental RMGICs. In conclusion, the experimental RMGICs showed comparable strength but lower cytotoxicity compared to the commercial RMGICs. These novel materials could be used as alternative materials for pulp protection. Full article

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

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17 pages, 4212 KiB

Open AccessArticle

Viscoelastic Behavior of Drug-Loaded Polyurethane

by Navideh Abbasnezhad, Mohammadali Shirinbayan, Fatiha Chabi, Stephane Champmartin, Abbas Tcharkhtchi and Farid Bakir

Polymers 2021, 13(16), 2608; https://doi.org/10.3390/polym13162608 - 5 Aug 2021

Cited by 3 | Viewed by 2595

Abstract

Drug-eluting stents are desirable platforms for local medicine delivery. However, the incorporation of drugs into polymers can influence the mechanical and physicochemical properties of said matrix, which is a topic that is still poorly understood. In fact, this is more noticeable since the apposition is most often accompanied by mechanical stresses on the polymer coating, which can induce therapeutic failure that can result in death. It is therefore necessary to better understand their behavior by examining their properties in conditions such as those in living beings. We studied polyurethane drug carriers made in-house. Diclofenac epolamine was chosen as a model hydrophilic medicine. We used thermal measurements (DMTA) and tensile tests. The aim was to establish the influence of the loading and release of the drug on the physicochemical properties of this polymer in the presence of a stagnant or circulating fluid medium, phosphate-buffered saline (PBS). For the two PU/drug loadings studied, the effect of the initial drug load was more marked. The free volume fraction and the number of pores in the samples increased with the increasing percent of the drug and with release time. The kinetic profiles were accelerated with the loading ratio and with the presence of flow. Young′s modulus and ultimate stress were not significantly influenced by the release time. A relevant relationship between the tensile properties and the viscoelastic behavior of the samples was developed. Our results have implications for optimizing the performance of drug coatings for stents. Full article

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

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22 pages, 3403 KiB

Open AccessArticle

Supercritical Impregnation of Ketoprofen into Polylactic Acid for Biomedical Application: Analysis and Modeling of the Release Kinetic

by Lidia Verano Naranjo, Cristina Cejudo Bastante, Lourdes Casas Cardoso, Casimiro Mantell Serrano and Enrique José Martínez de la Ossa Fernández

Polymers 2021, 13(12), 1982; https://doi.org/10.3390/polym13121982 - 17 Jun 2021

Cited by 19 | Viewed by 2959

Abstract

Ketoprofen (KET) is an anti-inflammatory drug often used in medicine due to its analgesic and antipyretic effects. If it is administered in a controlled form by means of different dosing devices, it acts throughout the patient’s recovery period improving its efficacy. This study intends to support the use of supercritical solvent impregnation (SSI) as an efficient technique to develop polylactic acid (PLA) functionalized with ketoprofen, for use as controlled drug release devices. For this purpose, firstly, the influence of different SSI variables on the desirable swelling of the polymer structure, while avoiding their foaming, were evaluated. Then, the resulting ketoprofen loading was evaluated under different pressure/temperature conditions. It was generally found that as pressure and temperature are higher, the drug impregnation loads also increase. The maximum impregnation loads (at about 9% KET/PLA) were obtained at 200 bar and 75 °C. In vitro drug release tests of the impregnated compound were also carried out, and it was found that drug release profiles were also dependent on the specific pressure and temperature conditions used for the impregnation of each polymer filament. Full article

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

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17 pages, 4806 KiB

Open AccessArticle

Development of a Model Based on Physical Mechanisms for the Explanation of Drug Release: Application to Diclofenac Release from Polyurethane Films

by Navideh Abbasnezhad, Mohamed Kebdani, Mohammadali Shirinbayan, Stéphane Champmartin, Abbas Tcharkhtchi, Smaine Kouidri and Farid Bakir

Polymers 2021, 13(8), 1230; https://doi.org/10.3390/polym13081230 - 10 Apr 2021

Cited by 19 | Viewed by 2946

Abstract

In this study, we present a method for prediction of the drug-release profile based on the physical mechanisms that can intervene in drug release from a drug-carrier. The application presented here incorporates the effects of drug concentration and Reynolds number defining the circulating flow in the testing vein. The experimental data used relate to the release of diclofenac from samples of non-degradable polyurethane subjected to static and continuous flow. This case includes simultaneously three mechanisms: burst-release, diffusion and osmotic pressure, identified beforehand here as being able to contribute to the drug liberation. For this purpose, authors coded the Sequential Quadratic Programming Algorithm to solve the problem of non-linear optimization. The experimental data used to develop the mathematical model obtained from release studies carried out in water solution at 37 °C, for three concentrations of diclofenac and two water flow rates. We discuss the contribution of mechanisms and kinetics by considering two aforementioned parameters and, following that, we obtain the specific-model and compare the calculated results with the experimental results for the reserved cases. The results showed that drug percentage mostly affect the burst release, however flow rate has affected the osmotic release. In addition, release kinetics of all the mechanisms have increased by increasing the values of two considered parameters. Full article

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

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22 pages, 2732 KiB

Open AccessSystematic Review

The Effect of Nanoparticle-Incorporated Natural-Based Biomaterials towards Cells on Activated Pathways: A Systematic Review

by Nur Izzah Md Fadilah, Isma Liza Mohd Isa, Wan Safwani Wan Kamarul Zaman, Yasuhiko Tabata and Mh Busra Fauzi

Polymers 2022, 14(3), 476; https://doi.org/10.3390/polym14030476 - 25 Jan 2022

Cited by 40 | Viewed by 5807

Abstract

The advancement of natural-based biomaterials in providing a carrier has revealed a wide range of benefits in the biomedical sciences, particularly in wound healing, tissue engineering and regenerative medicine. Incorporating nanoparticles within polymer composites has been reported to enhance scaffolding performance, cellular interactions and their physico-chemical and biological properties in comparison to analogue composites without nanoparticles. This review summarized the current knowledge of nanoparticles incorporated into natural-based biomaterials with effects on their cellular interactions in wound healing. Although the mechanisms of wound healing and the function of specific cells in wound repair have been partially described, many of the underlying signaling pathways remain unknown. We also reviewed the current understanding and new insights into the wingless/integrated (Wnt)/β-catenin pathway and other signaling pathways of transforming growth factor beta (TGF-β), Notch, and Sonic hedgehog during wound healing. The findings demonstrated that most of the studies reported positive outcomes of biomaterial scaffolds incorporated with nanoparticles on cell attachment, viability, proliferation, and migration. Combining therapies consisting of nanoparticles and biomaterials could be promising for future therapies and better outcomes in tissue engineering and regenerative medicine. Full article

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

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