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Biopolymers in Drug Delivery and Regenerative Medicine
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Biopolymers in Drug Delivery and Regenerative Medicine

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 37823

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Carlos A. García-González

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Guest Editor
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
Interests: aerogels; supercritical fluids; regenerative medicine; pharmaceutical technology; 3D-bioprinting; porous materials; scaffolds; biomedical applications
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pasquale Del Gaudio

E-Mail Website
Guest Editor
Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy
Interests: hydrogels; aerogels; controlled drug delivery; wound healing; carbohydrate polymers; microparticles; nanoparticles; nanocomposite; 3D printing
Special Issues, Collections and Topics in MDPI journals
Dr. Ricardo Starbird

E-Mail Website
Guest Editor
Escuela de Química, Instituto Tecnológico de Costa Rica, 30102 Cartago, PO Box 159-7050, Costa Rica
Interests: polymer science; structuration of biomass and conductive polymers; composites and electrochemical sensors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biopolymers including natural (e.g., polysaccharides, proteins, gums, natural rubbers, bacterial polymers), synthetic (e.g., aliphatic polyesters and polyphosphoester), and biocomposites are of paramount interest in regenerative medicine, due to their availability, processability, and low toxicity. Moreover, the structuration of biopolymer-based materials at the nano- and microscale along with their chemical properties are crucial in the engineering of advanced carriers for drug products. Finally, combination products including or based on biopolymers for controlled drug release offer a powerful solution to improve the tissue integration and biological response of these materials. Understanding the drug delivery mechanisms, efficiency, and toxicity of such systems may be useful for regenerative medicine and pharmaceutical technology.

The main aim of the Special Issue on “Biopolymers in Drug Delivery and Regenerative Medicine” is to gather recent findings and current advances on biopolymer research for biomedical applications, particularly in regenerative medicine, wound healing, and drug delivery. Contributions to this issue can be as original research or review articles and may cover all aspects of biopolymer research, ranging from the chemical synthesis and characterization of modified biopolymers, their processing in different morphologies and hierarchical structures, as well as their assessment for biomedical uses.

Prof. Pasquale Del Gaudio
Dr. Eng. Carlos A. García-González
Dr. Ricardo Starbird
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. Molecules 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

  • Biopolymer
  • Drug delivery
  • Regenerative medicine
  • Wound healing
  • Biodegradation
  • Nanostructured carriers

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 201 KiB  
Editorial
Special Issue: Biopolymers in Drug Delivery and Regenerative Medicine
by Ricardo Starbird-Perez, Pasquale Del Gaudio and Carlos A. García-González
Molecules 2021, 26(3), 568; https://doi.org/10.3390/molecules26030568 - 22 Jan 2021
Cited by 5 | Viewed by 2355
Abstract
Biopolymers and biocomposites have emerged as promising pathways to develop novel materials and substrates for biomedical applications [...] Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)

Research

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14 pages, 6224 KiB  
Article
Modeling of the Production of Lipid Microparticles Using PGSS® Technique
by Clara López-Iglesias, Enriqueta R. López, Josefa Fernández, Mariana Landin and Carlos A. García-González
Molecules 2020, 25(21), 4927; https://doi.org/10.3390/molecules25214927 - 24 Oct 2020
Cited by 11 | Viewed by 2505
Abstract
Solid lipid microparticles (SLMPs) are attractive carriers as delivery systems as they are stable, easy to manufacture and can provide controlled release of bioactive agents and increase their efficacy and/or safety. Particles from Gas-Saturated Solutions (PGSS®) technique is a solvent-free technology [...] Read more.
Solid lipid microparticles (SLMPs) are attractive carriers as delivery systems as they are stable, easy to manufacture and can provide controlled release of bioactive agents and increase their efficacy and/or safety. Particles from Gas-Saturated Solutions (PGSS®) technique is a solvent-free technology to produce SLMPs, which involves the use of supercritical CO2 (scCO2) at mild pressures and temperatures for the melting of lipids and atomization into particles. The determination of the key processing variables is crucial in PGSS® technique to obtain reliable and reproducible microparticles, therefore the modelling of SLMPs production process and variables control are of great interest to obtain quality therapeutic systems. In this work, the melting point depression of a commercial lipid (glyceryl monostearate, GMS) under compressed CO2 was studied using view cell experiments. Based on an unconstrained D-optimal design for three variables (nozzle diameter, temperature and pressure), SLMPs were produced using the PGSS® technique. The yield of production was registered and the particles characterized in terms of particle size distribution. Variable modeling was carried out using artificial neural networks and fuzzy logic integrated into neurofuzzy software. Modeling results highlight the main effect of temperature to tune the mean diameter SLMPs, whereas the pressure-nozzle diameter interaction is the main responsible in the SLMPs size distribution and in the PGSS® production yield. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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11 pages, 4429 KiB  
Article
Biobased Cryogels from Enzymatically Oxidized Starch: Functionalized Materials as Carriers of Active Molecules
by Antonella Caterina Boccia, Guido Scavia, Ilaria Schizzi and Lucia Conzatti
Molecules 2020, 25(11), 2557; https://doi.org/10.3390/molecules25112557 - 31 May 2020
Cited by 11 | Viewed by 2701
Abstract
Starch recovered from an agrifood waste, pea pods, was enzymatically modified and used to prepare cryogels applied as drug carriers. The enzymatic modification of starch was performed using the laccase/(2,2,6,6-tetramethylpiperidin-1-yl)oxyl TEMPO system, at a variable molar ratio. The characterization of the ensuing starches [...] Read more.
Starch recovered from an agrifood waste, pea pods, was enzymatically modified and used to prepare cryogels applied as drug carriers. The enzymatic modification of starch was performed using the laccase/(2,2,6,6-tetramethylpiperidin-1-yl)oxyl TEMPO system, at a variable molar ratio. The characterization of the ensuing starches by solution NMR spectroscopy showed partial conversion of the primary hydroxyl groups versus aldehyde and carboxyl groups and successive creation of hemiacetal and ester bonds. Enzymatically modified starch after simple freezing and lyophilization process provided stable and compact cryogels with a morphology characterized by irregular pores, as determined by atomic force (AFM) and scanning electron microscopy (SEM). The application of cryogels as carriers of active molecules was successfully evaluated by following two different approaches of loading with drugs: a) as loaded sponge, by adsorption of drug from the liquid phase; and b) as dry-loaded cryogel, from a dehydration step added to loaded cryogel from route (a). The efficiency of the two routes was studied and compared by determining the drug release profile by proton NMR studies over time. Preliminary results demonstrated that cryogels from modified starch are good candidates to act as drug delivery systems due to their stability and prolonged residence times of loaded molecules, opening promising applications in biomedical and food packaging scenarios. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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13 pages, 2393 KiB  
Article
Polysaccharide κ-Carrageenan as Doping Agent in Conductive Coatings for Electrochemical Controlled Release of Dexamethasone at Therapeutic Doses
by Karla Ramírez Sánchez, Aura Ledezma-Espinoza, Andrés Sánchez-Kopper, Esteban Avendaño-Soto, Mónica Prado and Ricardo Starbird Perez
Molecules 2020, 25(9), 2139; https://doi.org/10.3390/molecules25092139 - 03 May 2020
Cited by 5 | Viewed by 3236
Abstract
Smart conductive materials are developed in regenerative medicine to promote a controlled release profile of charged bioactive agents in the vicinity of implants. The incorporation and the active electrochemical release of the charged compounds into the organic conductive coating is achieved due to [...] Read more.
Smart conductive materials are developed in regenerative medicine to promote a controlled release profile of charged bioactive agents in the vicinity of implants. The incorporation and the active electrochemical release of the charged compounds into the organic conductive coating is achieved due to its intrinsic electrical properties. The anti-inflammatory drug dexamethasone was added during the polymerization, and its subsequent release at therapeutic doses was reached by electrical stimulation. In this work, a Poly (3,4-ethylenedioxythiophene): κ-carrageenan: dexamethasone film was prepared, and κ-carrageenan was incorporated to keep the electrochemical and physical stability of the electroactive matrix. The presence of κ-carrageenan and dexamethasone in the conductive film was confirmed by µ-Raman spectroscopy and their effect in the topographic was studied using profilometry. The dexamethasone release process was evaluated by cyclic voltammetry and High-Resolution mass spectrometry. In conclusion, κ-carrageenan as a doping agent improves the electrical properties of the conductive layer allowing the release of dexamethasone at therapeutic levels by electrochemical stimulation, providing a stable system to be used in organic bioelectronics systems. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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19 pages, 3010 KiB  
Article
Aerogels from Cellulose Phosphates of Low Degree of Substitution: A TBAF·H2O/DMSO Based Approach
by Christian B. Schimper, Paul S. Pachschwoell, Hubert Hettegger, Marie-Alexandra Neouze, Jean-Marie Nedelec, Martin Wendland, Thomas Rosenau and Falk Liebner
Molecules 2020, 25(7), 1695; https://doi.org/10.3390/molecules25071695 - 07 Apr 2020
Cited by 6 | Viewed by 3032
Abstract
Biopolymer aerogels of appropriate open-porous morphology, nanotopology, surface chemistry, and mechanical properties can be promising cell scaffolding materials. Here, we report a facile approach towards the preparation of cellulose phosphate aerogels from two types of cellulosic source materials. Since high degrees of phosphorylation [...] Read more.
Biopolymer aerogels of appropriate open-porous morphology, nanotopology, surface chemistry, and mechanical properties can be promising cell scaffolding materials. Here, we report a facile approach towards the preparation of cellulose phosphate aerogels from two types of cellulosic source materials. Since high degrees of phosphorylation would afford water-soluble products inappropriate for cell scaffolding, products of low DSP (ca. 0.2) were prepared by a heterogeneous approach. Aiming at both i) full preservation of chemical integrity of cellulose during dissolution and ii) utilization of specific phase separation mechanisms upon coagulation of cellulose, TBAF·H2O/DMSO was employed as a non-derivatizing solvent. Sequential dissolution of cellulose phosphates, casting, coagulation, solvent exchange, and scCO2 drying afforded lightweight, nano-porous aerogels. Compared to their non-derivatized counterparts, cellulose phosphate aerogels are less sensitive towards shrinking during solvent exchange. This is presumably due to electrostatic repulsion and translates into faster scCO2 drying. The low DSP values have no negative impact on pore size distribution, specific surface (SBET ≤ 310 m2 g−1), porosity (Π 95.5–97 vol.%), or stiffness (Eρ ≤ 211 MPa cm3 g−1). Considering the sterilization capabilities of scCO2, existing templating opportunities to afford dual-porous scaffolds and the good hemocompatibility of phosphorylated cellulose, TBAF·H2O/DMSO can be regarded a promising solvent system for the manufacture of cell scaffolding materials. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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12 pages, 1891 KiB  
Article
Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
by Emily Goel, Megan Erwin, Claire V. Cawthon, Carson Schaff, Nathaniel Fedor, Trevor Rayl, Onree Wilson, Uwe Christians, Thomas C. Register, Randolph L. Geary, Justin Saul and Saami K. Yazdani
Molecules 2020, 25(7), 1596; https://doi.org/10.3390/molecules25071596 - 31 Mar 2020
Cited by 9 | Viewed by 4087
Abstract
Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to [...] Read more.
Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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14 pages, 5127 KiB  
Article
Preparation and Characterization of Chitosan-Coated Pectin Aerogels: Curcumin Case Study
by Milica Pantić, Gabrijela Horvat, Željko Knez and Zoran Novak
Molecules 2020, 25(5), 1187; https://doi.org/10.3390/molecules25051187 - 06 Mar 2020
Cited by 24 | Viewed by 3275
Abstract
The following study describes the preparation of pectin aerogels and pectin aerogels coated with an external layer of chitosan. For the preparation of chitosan-coated pectin aerogels, a modified coating procedure was employed. Since pectin as well as pectin aerogels are highly water soluble, [...] Read more.
The following study describes the preparation of pectin aerogels and pectin aerogels coated with an external layer of chitosan. For the preparation of chitosan-coated pectin aerogels, a modified coating procedure was employed. Since pectin as well as pectin aerogels are highly water soluble, a function of chitosan coating is to slow down the dissolution of pectin and consequently the release of the active substances. Textural properties, surface morphologies, thermal properties, and functional groups of prepared aerogels were determined. Results indicated that the coating procedure affected the textural properties of pectin aerogels, resulting in smaller specific surface areas of 276 m2/g, compared to 441 m2/g. However, chitosan-coated pectin aerogels still retained favorable properties for carriers of active substances. The case study for prepared aerogels was conducted with curcumin. Prior to in-vitro release studies, swelling studies were performed. Curcumin’s dissolution from both aerogels showed to be successful. Pectin aerogels released curcumin in 3 h showing a burst release profile. Chitosan-coated pectin aerogels prolonged curcumin release up to 24 h, thus showing a controlled release profile. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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Review

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21 pages, 3786 KiB  
Review
Smart Porous Multi-Stimulus Polysaccharide-Based Biomaterials for Tissue Engineering
by Fernando Alvarado-Hidalgo, Karla Ramírez-Sánchez and Ricardo Starbird-Perez
Molecules 2020, 25(22), 5286; https://doi.org/10.3390/molecules25225286 - 13 Nov 2020
Cited by 10 | Viewed by 4024
Abstract
Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to [...] Read more.
Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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36 pages, 8806 KiB  
Review
Technologies and Formulation Design of Polysaccharide-Based Hydrogels for Drug Delivery
by Giulia Auriemma, Paola Russo, Pasquale Del Gaudio, Carlos A. García-González, Mariana Landín and Rita Patrizia Aquino
Molecules 2020, 25(14), 3156; https://doi.org/10.3390/molecules25143156 - 10 Jul 2020
Cited by 49 | Viewed by 6340
Abstract
Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their [...] Read more.
Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their proper release and targeting. This review discusses the different phases involved in the production of PbHPs in pharmaceutical technology, such as droplet formation (SOL phase), sol-gel transition of the droplets (GEL phase) and drying, as well as the different methods available for droplet production with a special focus on prilling technique. In addition, an overview of the various droplet gelation methods with particular emphasis on ionic cross-linking of several polysaccharides enabling the formation of particles with inner highly porous network or nanofibrillar structure is given. Moreover, a detailed survey of the different inner texture, in xerogels, cryogels or aerogels, each with specific arrangement and properties, which can be obtained with different drying methods, is presented. Various case studies are reported to highlight the most appropriate application of such systems in pharmaceutical field. We also describe the challenges to be faced for the breakthrough towards clinic studies and, finally, the market, focusing on the useful approach of safety-by-design (SbD). Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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35 pages, 3813 KiB  
Review
Recent Advances in Polymer Nanomaterials for Drug Delivery of Adjuvants in Colorectal Cancer Treatment: A Scientific-Technological Analysis and Review
by Marlon Osorio, Estefanía Martinez, Tonny Naranjo and Cristina Castro
Molecules 2020, 25(10), 2270; https://doi.org/10.3390/molecules25102270 - 12 May 2020
Cited by 13 | Viewed by 4489
Abstract
Colorectal cancer (CRC) is the type with the second highest morbidity. Recently, a great number of bioactive compounds and encapsulation techniques have been developed. Thus, this paper aims to review the drug delivery strategies for chemotherapy adjuvant treatments for CRC, including an initial [...] Read more.
Colorectal cancer (CRC) is the type with the second highest morbidity. Recently, a great number of bioactive compounds and encapsulation techniques have been developed. Thus, this paper aims to review the drug delivery strategies for chemotherapy adjuvant treatments for CRC, including an initial scientific-technological analysis of the papers and patents related to cancer, CRC, and adjuvant treatments. For 2018, a total of 167,366 cancer-related papers and 306,240 patents were found. Adjuvant treatments represented 39.3% of the total CRC patents, indicating the importance of adjuvants in the prognosis of patients. Chemotherapy adjuvants can be divided into two groups, natural and synthetic (5-fluorouracil and derivatives). Both groups can be encapsulated using polymers. Polymer-based drug delivery systems can be classified according to polymer nature. From those, anionic polymers have garnered the most attention, because they are pH responsive. The use of polymers tailors the desorption profile, improving drug bioavailability and enhancing the local treatment of CRC via oral administration. Finally, it can be concluded that antioxidants are emerging compounds that can complement today’s chemotherapy treatments. In the long term, encapsulated antioxidants will replace synthetic drugs and will play an important role in curing CRC. Full article
(This article belongs to the Special Issue Biopolymers in Drug Delivery and Regenerative Medicine)
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