Emerging Strategies to Improve the Design and Manufacturing of Biocompatible Therapeutic Materials

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 38641

Special Issue Editors


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Guest Editor
Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville. C/ Profesor Garcia Gonzalez, 2, 41012 Seville, Spain
Interests: polymer chemistry; biodegradable polymers; drug delivery systems; inkjet 3D printing; additive manufacturing
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Guest Editor
Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Seville, C/Profesor García González, 2, 41012 Seville, Spain
Interests: coating materials; materials for prosthesis; polymers or gels for biomedicine; synthesis of potentially bioactive entities; modeling and drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, the field of medicine is drastically increasing its results, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the LADME (liberation, absorption, distribution, metabolism and excretion) properties of the derived formulations, with a consequent enhancement of the treatment efficacy, a reduction in the secondary effects, and a better compliance with the dosage guidelines. On the other hand, the utilization of biocompatible scaffolds is translating into the possibility of regenerating biological tissues. Additionally, personalized medicine is benefiting from the advantages offered by additive manufacturing. However, all these areas have in common the need to develop novel materials or composites that fulfill the requirements of each application.

Therefore, this Special Issue aims to identify novel materials/composites that have been developed with specific characteristics to accomplish the biomedical application for which they were designed.

Dr. Belén Begines
Dr. Ana Alcudia
Guest Editors

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Keywords

  • personalized medicine
  • nanomedicine
  • controlled release
  • antibacterial/antimicrobial activity
  • biodegradable hydrogels
  • micro and nanoparticles
  • biomaterials
  • biodegradable polymers
  • biocompatible coatings
  • nanocomposites
  • porous materials
  • modelling
  • encapsulation
  • additive manufacturing
  • 3D printing
  • prothesis
  • scaffolds
  • tissue targeting

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Published Papers (10 papers)

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Editorial

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5 pages, 219 KiB  
Editorial
Emerging Strategies to Improve the Design and Manufacturing of Biocompatible Therapeutic Materials
by Guillermo Martínez, Juan Vázquez, Belén Begines and Ana Alcudia
Pharmaceutics 2023, 15(7), 1938; https://doi.org/10.3390/pharmaceutics15071938 - 12 Jul 2023
Viewed by 1183
Abstract
Currently, the field of medicine is drastically advancing, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the liberation, absorption, [...] Read more.
Currently, the field of medicine is drastically advancing, mainly due to the progress in emerging areas such as nanomedicine, regenerative medicine, and personalized medicine. For example, the development of novel drug delivery systems in the form of nanoparticles is improving the liberation, absorption, distribution, metabolism, and excretion (LADME) properties of the derived formulations, with a consequent enhancement in the treatment efficacy, a reduction in the secondary effects, and an increase in compliance with the dosage guidelines. Additionally, the use of biocompatible scaffolds is translating into the possibility of regenerating biological tissues. Personalized medicine is also benefiting from the advantages offered by additive manufacturing. However, all these areas have in common the need to develop novel materials or composites that fulfill the requirements of each application. Therefore, the aim of this Special Issue was to identify novel materials/composites that have been developed with specific characteristics for the designed biomedical application. Full article

Research

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13 pages, 5165 KiB  
Article
Development of Plant Protein Derived Tri Angular Shaped Nano Zinc Oxide Particles with Inherent Antibacterial and Neurotoxicity Properties
by Tianyu Hou, Siva Sankar Sana, Huizhen Li, Xin Wang, Qinqin Wang, Vijaya Kumar Naidu Boya, Ramakrishna Vadde, Raj Kumar, Divya Vishambhar Kumbhakar, Zhijun Zhang and Narsimha Mamidi
Pharmaceutics 2022, 14(10), 2155; https://doi.org/10.3390/pharmaceutics14102155 - 10 Oct 2022
Cited by 12 | Viewed by 2840
Abstract
The synthesis of nanometer-sized metallic nanoparticles utilizing bio-sources is one of the most cost-effective and ecologically friendly approaches. Nano-zinc oxide particles (N-ZnO Ps) were made using a simple green synthesis method using an aqueous zinc nitrate salt and Perilla frutescens crude protein as [...] Read more.
The synthesis of nanometer-sized metallic nanoparticles utilizing bio-sources is one of the most cost-effective and ecologically friendly approaches. Nano-zinc oxide particles (N-ZnO Ps) were made using a simple green synthesis method using an aqueous zinc nitrate salt and Perilla frutescens crude protein as a protecting and reducing agent in the current work. UV-visible (UV-vis) spectrophotometry, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), (energy dispersive x-ray spectroscopy) EDX and high-resolution transmission electron microscopy (HR-TEM) were used to characterize the synthesized N-ZnO Ps. A distinctive UV-vis absorption peak was observed at 370 nm due to N-ZnO Ps. The SEM and HR-TEM pictures revealed N-ZnO Ps with a triangular form. The XRD pattern indicated the wurtzite structure of N-ZnO Ps. Nanoparticles exhibited a zeta potential of −11.3 mV. The antibacterial activity of N-ZnO Ps was tested against Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumonia) microorganisms. The N-ZnO Ps were non-toxic to HMC-3 human normal brain microglia cells; however, they exhibited a potential cytotoxic effect on the LN-18 human brain glioblastoma cell line. These results indicate that N-ZnOPs can act as promising antibacterial and anticancer treatments in the prevention of Glioblastoma. Full article
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18 pages, 722 KiB  
Article
Synthesis and Characterization of a Novel Composite Scaffold Based on Hyaluronic Acid and Equine Type I Collagen
by Erwin Pavel Lamparelli, Veronica Casagranda, Daniele Pressato, Nicola Maffulli, Giovanna Della Porta and Davide Bellini
Pharmaceutics 2022, 14(9), 1752; https://doi.org/10.3390/pharmaceutics14091752 - 23 Aug 2022
Cited by 8 | Viewed by 3324
Abstract
Herein, the synthesis and characterization of a novel composite biopolymer scaffold—based on equine type I collagen and hyaluronic acid—were described by using a reaction in heterogeneous phase. The resulting biomimetic structure was characterized in terms of chemical, physical, and cytotoxicity properties using human-derived [...] Read more.
Herein, the synthesis and characterization of a novel composite biopolymer scaffold—based on equine type I collagen and hyaluronic acid—were described by using a reaction in heterogeneous phase. The resulting biomimetic structure was characterized in terms of chemical, physical, and cytotoxicity properties using human-derived lymphocytes and chondrocytes. Firstly, FT-IR data proved a successful reticulation of hyaluronic acid within collagen structure with the appearance of a new peak at a wavenumber of 1735 cm−1 associated with ester carbonyl stretch. TGA and DSC characterizations confirmed different thermal stability of cross-linked scaffolds while morphological analysis by scanning electron microscopy (SEM) suggested the presence of a highly porous structure with open and interconnected void areas suitable for hosting cells. The enzymatic degradation profile confirmed scaffold higher endurance with collagenase as compared with collagen alone. However, it was particularly interesting that the mechanical behavior of the composite scaffold showed an excellent shape memory, especially when it was hydrated, with an improved Young’s modulus of 9.96 ± 0.53 kPa (p ≤ 0.001) as well as a maximum load at 97.36 ± 3.58 kPa compared to the simple collagen scaffold that had a modulus of 1.57 ± 0.08 kPa and a maximum load of 36.91 ± 0.24 kPa. Finally, in vitro cytotoxicity confirmed good product safety with human lymphocytes (viability of 81.92 ± 1.9 and 76.37 ± 1.2 after 24 and 48 h, respectively), whereas excellent gene expression profiles of chondrocytes with a significant upregulation of SOX9 and ACAN after 10 days of culture indicated our scaffold’s ability of preserving chondrogenic phenotype. The described material could be considered a potential tool to be implanted in patients with cartilage defects. Full article
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17 pages, 3895 KiB  
Article
Novel Utilization of Therapeutic Coatings Based on Infiltrated Encapsulated Rose Bengal Microspheres in Porous Titanium for Implant Applications
by Francesca Accioni, Giovanna Rassu, Belén Begines, Luisa Marleny Rodríguez-Albelo, Yadir Torres, Ana Alcudia and Elisabetta Gavini
Pharmaceutics 2022, 14(6), 1244; https://doi.org/10.3390/pharmaceutics14061244 - 12 Jun 2022
Cited by 6 | Viewed by 2762
Abstract
Despite the increasing progress achieved in the last 20 years in both the fabrication of porous dental implants and the development of new biopolymers for targeting drug therapy, there are important issues such as bone resorption, poor osseointegration, and bacterial infections that remain [...] Read more.
Despite the increasing progress achieved in the last 20 years in both the fabrication of porous dental implants and the development of new biopolymers for targeting drug therapy, there are important issues such as bone resorption, poor osseointegration, and bacterial infections that remain as critical challenges to avoid clinical failure problems. In this work, we present a novel microtechnology based on polycaprolactone microspheres that can adhere to porous titanium implant models obtained by the spacer holder technique to allow a custom biomechanical and biofunctional balance. For this purpose, a double emulsion solvent evaporation technique was successfully employed for the fabrication of the microparticles properly loaded with the antibacterial therapeutic agent, rose bengal. The resulting microspheres were infiltrated into porous titanium substrate and sintered at 60 °C for 1 h, obtaining a convenient prophylactic network. In fact, the sintered polymeric microparticles were demonstrated to be key to controlling the drug dissolution rate and favoring the early healing process as consequence of a better wettability of the porous titanium substrate to promote calcium phosphate nucleation. Thus, this joint technology proposes a suitable prophylactic tool to prevent both early-stage infection and late-stage osseointegration problems. Full article
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21 pages, 4601 KiB  
Article
Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems
by Carmen Moya-Lopez, Alberto Juan, Murillo Donizeti, Jesus Valcarcel, José A. Vazquez, Eduardo Solano, David Chapron, Patrice Bourson, Ivan Bravo, Carlos Alonso-Moreno, Pilar Clemente-Casares, Carlos Gracia-Fernández, Alessandro Longo, Georges Salloum-Abou-Jaoude, Alberto Ocaña, Manuel M. Piñeiro, Carolina Hermida-Merino and Daniel Hermida-Merino
Pharmaceutics 2022, 14(6), 1138; https://doi.org/10.3390/pharmaceutics14061138 - 27 May 2022
Cited by 10 | Viewed by 3378
Abstract
A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired [...] Read more.
A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect. The nanoparticles generated were successfully formulated with two different antitumoral compounds (doxorubicin and dasatinib) possessing different structures to prove the loading versatility of the drug delivery system. The bionanocomposites were characterized by several techniques (SEM, DLS, RAMAN, DSC, SAXS/WAXS and rheology) as well as their reversible sol–gel transition upon thermal treatment that occurs during the drug delivery system preparation and the thermal annealing step. In addition, the local applicability of the drug delivery system was assessed by the so-called “syringe test” to validate both the storage capability and its flow properties at simulated physiological conditions. Finally, the drug release profiles of the doxorubicin from both the PLA nanoparticles or the bionanocomposites were analyzed and correlated to the nanostructure of the drug delivery system. Full article
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18 pages, 3274 KiB  
Article
Antimicrobial Properties of Amino-Acid-Derived N-Heterocyclic Carbene Silver Complexes
by Adrián Sánchez, Carlos J. Carrasco, Francisco Montilla, Eleuterio Álvarez, Agustín Galindo, María Pérez-Aranda, Eloísa Pajuelo and Ana Alcudia
Pharmaceutics 2022, 14(4), 748; https://doi.org/10.3390/pharmaceutics14040748 - 30 Mar 2022
Cited by 10 | Viewed by 2481
Abstract
Complexes {Ag[NHCMes,R]}n (R = H, 2a; Me, 2b and 2b’; iPr, 2c; iBu, 2d), were prepared by treatment of imidazolium precursor compounds [ImMes,R] (2-(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1a, (S)-2-alkyl [...] Read more.
Complexes {Ag[NHCMes,R]}n (R = H, 2a; Me, 2b and 2b’; iPr, 2c; iBu, 2d), were prepared by treatment of imidazolium precursor compounds [ImMes,R] (2-(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1a, (S)-2-alkyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1bd, and (R)-2-methyl(3-mesityl-1H-imidazol-3-ium-1-yl)acetate, 1b’, with Ag2O under appropriate conditions. They were characterised by analytical, spectroscopic (IR, 1H, and 13C NMR and polarimetry), and X-ray methods (2a). In the solid state, 2a is a one-dimensional coordination polymer, in which the silver(I) cation is bonded to the carbene ligand and to the carboxylate group of a symmetry-related Ag[NHCMes,H] moiety. The coordination environment of the silver centre is well described by the DFT study of the dimeric model {Ag[NHCMes,H]}2. The antimicrobial properties of these complexes were evaluated versus Gram-negative bacteria E. coli and P. aeruginosa. From the observed MIC and MBC values (minimal inhibitory concentration and minimal bactericidal concentration, respectively), complex 2b’ showed the best antimicrobial properties (eutomer), which were significantly better than those of its enantiomeric derivative 2b (distomer). Additionally, analysis of MIC and MBC values of 2ad reveal a clear structure–antimicrobial effect relationship. Antimicrobial activity decreases when the steric properties of the R alkyl group in {Ag[NHCMes,R]}n increase. Full article
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16 pages, 3205 KiB  
Article
Mini Cleanroom for the Manufacture of Advanced Therapy Medicinal Products (ATMP): Bioengineered Corneal Epithelium
by Silvia Berisa-Prado, Natalia Vázquez, Manuel Chacón, Mairobi Persinal-Medina, Sergio Alonso-Alonso, Begoña Baamonde, José F. Alfonso, Luis Fernández-Vega-Cueto, Jesús Merayo-Lloves and Álvaro Meana
Pharmaceutics 2021, 13(8), 1282; https://doi.org/10.3390/pharmaceutics13081282 - 17 Aug 2021
Cited by 2 | Viewed by 2382
Abstract
Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B [...] Read more.
Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B environment). This makes ATMP expensive. Moreover, the production of many of these therapeutic products may also be unprofitable, as in most cases their use is limited to a few patients and to a single batch per manufacturing unit. To reduce costs, ATMP may be produced in a scaled-down system isolated from the external environment (isolator), allowing for placement of this facility in a Class D environment, which is much more permissive and less costly. In this work, we confirm that it is possible to manufacture bioengineered corneal epithelium inside an isolator while fulfilling all the safety assurance standards at an affordable cost for patients. This small-scale ultra-clean working environment complies with GMP guidelines and could be a solution for the high costs associated with conventional cleanroom ATMP production. Full article
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19 pages, 4487 KiB  
Article
Osseointegration Improvement of Co-Cr-Mo Alloy Produced by Additive Manufacturing
by Amilton Iatecola, Guilherme Arthur Longhitano, Luiz Henrique Martinez Antunes, André Luiz Jardini, Emilio de Castro Miguel, Miloslav Béreš, Carlos Salles Lambert, Tiago Neves Andrade, Rogério Leone Buchaim, Daniela Vieira Buchaim, Karina Torres Pomini, Jefferson Aparecido Dias, Daniele Raineri Mesquita Serva Spressão, Marcílio Felix, Guinea Brasil Camargo Cardoso and Marcelo Rodrigues da Cunha
Pharmaceutics 2021, 13(5), 724; https://doi.org/10.3390/pharmaceutics13050724 - 14 May 2021
Cited by 16 | Viewed by 4752
Abstract
Cobalt-base alloys (Co-Cr-Mo) are widely employed in dentistry and orthopedic implants due to their biocompatibility, high mechanical strength and wear resistance. The osseointegration of implants can be improved by surface modification techniques. However, complex geometries obtained by additive manufacturing (AM) limits the efficiency [...] Read more.
Cobalt-base alloys (Co-Cr-Mo) are widely employed in dentistry and orthopedic implants due to their biocompatibility, high mechanical strength and wear resistance. The osseointegration of implants can be improved by surface modification techniques. However, complex geometries obtained by additive manufacturing (AM) limits the efficiency of mechanical-based surface modification techniques. Therefore, plasma immersion ion implantation (PIII) is the best alternative, creating nanotopography even in complex structures. In the present study, we report the osseointegration results in three conditions of the additively manufactured Co-Cr-Mo alloy: (i) as-built, (ii) after PIII, and (iii) coated with titanium (Ti) followed by PIII. The metallic samples were designed with a solid half and a porous half to observe the bone ingrowth in different surfaces. Our results revealed that all conditions presented cortical bone formation. The titanium-coated sample exhibited the best biomechanical results, which was attributed to the higher bone ingrowth percentage with almost all medullary canals filled with neoformed bone and the pores of the implant filled and surrounded by bone ingrowth. It was concluded that the metal alloys produced for AM are biocompatible and stimulate bone neoformation, especially when the Co-28Cr-6Mo alloy with a Ti-coated surface, nanostructured and anodized by PIII is used, whose technology has been shown to increase the osseointegration capacity of this implant. Full article
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Review

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30 pages, 13196 KiB  
Review
A Comprehensive Review of Patented Technologies to Fabricate Orodispersible Films: Proof of Patent Analysis (2000–2020)
by Maram Suresh Gupta, Devegowda Vishakante Gowda, Tegginamath Pramod Kumar and Jessica M. Rosenholm
Pharmaceutics 2022, 14(4), 820; https://doi.org/10.3390/pharmaceutics14040820 - 8 Apr 2022
Cited by 12 | Viewed by 5352
Abstract
Orodispersible films (ODFs)are ultra-thin, stamp-sized, rapidly disintegrating, and attractive oral drug delivery dosage forms best suited for the pediatric and geriatric patient populations. They can be fabricated by different techniques, but the most popular, simple, and industrially applicable technique is the solvent casting [...] Read more.
Orodispersible films (ODFs)are ultra-thin, stamp-sized, rapidly disintegrating, and attractive oral drug delivery dosage forms best suited for the pediatric and geriatric patient populations. They can be fabricated by different techniques, but the most popular, simple, and industrially applicable technique is the solvent casting method (SCM). In addition, they can also be fabricated by extrusion, printing, electrospinning, and by a combination of these technologies (e.g., SCM + printing). The present review is aimed to provide a comprehensive overview of patented technologies of the last two decades to fabricate ODFs. Through this review, we present evidence to adamantly confirm that SCM is the most popular method while electrospinning is the most recent and upcoming method to fabricate ODFs. We also speculate around the more patent-protected technologies especially in the domain of printing (two or three-dimensional), extrusion (ram or hot-melt extrusion), and electrospinning, or a combination of the methods thereof. Full article
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38 pages, 4503 KiB  
Review
Latest Trends in Surface Modification for Dental Implantology: Innovative Developments and Analytical Applications
by Francesca Accioni, Juan Vázquez, Manuel Merinero, Belén Begines and Ana Alcudia
Pharmaceutics 2022, 14(2), 455; https://doi.org/10.3390/pharmaceutics14020455 - 21 Feb 2022
Cited by 50 | Viewed by 8806
Abstract
An increase in the world population and its life expectancy, as well as the ongoing concern about our physical appearance, have elevated the relevance of dental implantology in recent decades. Engineering strategies to improve the survival rate of dental implants have been widely [...] Read more.
An increase in the world population and its life expectancy, as well as the ongoing concern about our physical appearance, have elevated the relevance of dental implantology in recent decades. Engineering strategies to improve the survival rate of dental implants have been widely investigated, focusing on implant material composition, geometry (usually guided to reduce stiffness), and interface surrounding tissues. Although efforts to develop different implant surface modifications are being applied in commercial dental prostheses today, the inclusion of surface coatings has gained special interest, as they can be tailored to efficiently enhance osseointegration, as well as to reduce bacterial-related infection, minimizing peri-implantitis appearance and its associated risks. The use of biomaterials to replace teeth has highlighted the need for the development of reliable analytical methods to assess the therapeutic benefits of implants. This literature review considers the state-of-the-art strategies for surface modification or coating and analytical methodologies for increasing the survival rate for teeth restoration. Full article
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