Research

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18 pages, 3683 KiB

Open AccessArticle

Evaluation and Optimization of Prolonged Release Mucoadhesive Tablets of Dexamethasone for Wound Healing: In Vitro–In Vivo Profiling in Healthy Volunteers

by Qurrat ul Ain Javed, Muhammad Ali Syed, Rabia Arshad, Abbas Rahdar, Muhammad Irfan, Syed Atif Raza, Gul Shahnaz, Sana Hanif and Ana M. Díez-Pascual

Pharmaceutics 2022, 14(4), 807; https://doi.org/10.3390/pharmaceutics14040807 - 07 Apr 2022

Cited by 9 | Viewed by 2716

Abstract

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1–Q7) were synthesized via direct compression method by varying the concentrations [...] Read more.

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1–Q7) were synthesized via direct compression method by varying the concentrations of polymers, i.e., ethyl cellulose (EC) and agar extract (AG). Moreover, the mucoadhesive polymeric tablets were characterized via physicochemical, in vitro, ex vivo and in vivo experiments. However, physicochemical characteristics such as FTIR showed no interaction with different polymeric combination. Surface pH of all formulations was normal to slightly alkaline. Highest hydration of up to 6.22% and swelling index was comprehended with maximum concentration of AG (50% of total tablet weight). Whereas, ex vivo and in vivo residence time and mucoadhesion were attributed to the increased concentrations of polymers. Moreover, Q7, (optimized formulation), containing 10% of EC and 40% of AG, exhibited maximum release of DXM (100%) over 8 h, along with sufficient mucoadhesive strength up to 11.73 g, following first-order kinetics having r² value of 0.9778. Hemostatic effects and epithelialization for triggering and promoting wound healing were highly pronounced in cases of Q7. Furthermore, in vivo residence time was 7.84 h followed by salivary drug concentration (4.2 µg/mL). However, mucoadhesive buccal tablets showed stability for 6 months, thus following the standardization (ICH-Iva) stability zone. In summary, DXM mucoadhesive tablets seem to be an ideal candidate for eradication of wound infections via local targeted delivery. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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23 pages, 8259 KiB

Open AccessEditor’s ChoiceArticle

Tailoring of Novel Azithromycin-Loaded Zinc Oxide Nanoparticles for Wound Healing

by Mohammed S. Saddik, Mahmoud M. A. Elsayed, Mohamed A. El-Mokhtar, Haitham Sedky, Jelan A. Abdel-Aleem, Ahmed M. Abu-Dief, Mostafa F. Al-Hakkani, Hazem L. Hussein, Samah A. Al-Shelkamy, Fatma Y. Meligy, Ali Khames and Heba A. Abou-Taleb

Pharmaceutics 2022, 14(1), 111; https://doi.org/10.3390/pharmaceutics14010111 - 05 Jan 2022

Cited by 64 | Viewed by 4905

Abstract

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates [...] Read more.

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box–Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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20 pages, 5195 KiB

Open AccessArticle

Imination of Microporous Chitosan Fibers—A Route to Biomaterials with “On Demand” Antimicrobial Activity and Biodegradation for Wound Dressings

by Alexandru Anisiei, Irina Rosca, Andreea-Isabela Sandu, Adrian Bele, Xinjian Cheng and Luminita Marin

Pharmaceutics 2022, 14(1), 117; https://doi.org/10.3390/pharmaceutics14010117 - 04 Jan 2022

Cited by 18 | Viewed by 2386

Abstract

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers’ characterization [...] Read more.

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers’ characterization was undertaken keeping in mind their application to wound healing. Thus, by FTIR and ¹H-NMR spectroscopy, it was confirmed the successful imination of the fibers and the conversion degree of the amine groups of chitosan into imine units. The fiber morphology in terms of fiber diameter, crystallinity, inter- and intra-fiber porosity and strength of intermolecular forces was investigated using scanning electron microscopy, polarized light microscopy, water vapor sorption and thermogravimetric analysis. The swelling ability was estimated in water and phosphate buffer by calculating the mass equilibrium swelling. The fiber biodegradation was explored in five media of different pH, corresponding to different stages of wound healing and the antimicrobial activity against the opportunistic pathogens inflicting wound infection was investigated according to standard tests. The biocompatibility and bioadhesivity were studied on normal human dermal fibroblast cells by direct contact procedure. The dynamic character of the imine linkage of the functionalized fibers was monitored by UV-vis spectroscopy. The results showed that the functionalization of the chitosan microporous nanofibers with antimicrobial agents via imine linkage is a great route towards bio-absorbable wound dressings with “on demand” antimicrobial properties and biodegradation rate matching the healing stages. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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16 pages, 12256 KiB

Open AccessArticle

Bacterial Cellulose as a Potential Bio-Scaffold for Effective Re-Epithelialization Therapy

by Juin-Hong Cherng, Sheng-Chieh Chou, Chin-Li Chen, Yi-Wen Wang, Shu-Jen Chang, Gang-Yi Fan, Fang-Shiuan Leung and En Meng

Pharmaceutics 2021, 13(10), 1592; https://doi.org/10.3390/pharmaceutics13101592 - 30 Sep 2021

Cited by 19 | Viewed by 2202

Abstract

Currently, there are several therapeutic approaches available for wound injury management. However, a better understanding of the underlying mechanisms of how biomaterials affect cell behavior is needed to develop potential repair strategies. Bacterial cellulose (BC) is a bacteria-produced biopolymer with several advantageous qualities [...] Read more.

Currently, there are several therapeutic approaches available for wound injury management. However, a better understanding of the underlying mechanisms of how biomaterials affect cell behavior is needed to develop potential repair strategies. Bacterial cellulose (BC) is a bacteria-produced biopolymer with several advantageous qualities for skin tissue engineering. The aim here was to investigate BC-based scaffold on epithelial regeneration and wound healing by examining its effects on the expression of scavenger receptor-A (SR-A) and underlying macrophage behavior. Full-thickness skin wounds were generated on Sprague-Dawley rats and the healing of these wounds, with and without BC scaffolds, was examined over 14 days using Masson’s trichome staining. BC scaffolds displayed excellent in vitro biocompatibility, maintained the stemness function of cells and promoted keratinocyte differentiation of cells, which are vital in maintaining and restoring the injured epidermis. BC scaffolds also exhibited positive in vivo effects on the wound microenvironment, including improved skin extracellular matrix deposition and controlled excessive inflammation by reduction of SR-A expression. Furthermore, BC scaffold significantly enhanced epithelialization by stimulating the balance of M1/M2 macrophage re-programming for beneficial tissue repair relative to that of collagen material. These findings suggest that BC-based materials are promising products for skin injury repair. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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17 pages, 5109 KiB

Open AccessArticle

Whey Proteins–Zinc Oxide Bionanocomposite as Antibacterial Films

by Paolo Pino, Silvia Ronchetti, Chiara Mollea, Marco Sangermano, Barbara Onida and Francesca Bosco

Pharmaceutics 2021, 13(9), 1426; https://doi.org/10.3390/pharmaceutics13091426 - 08 Sep 2021

Cited by 13 | Viewed by 2278

Abstract

The use of toxic crosslinking agents and reagents in the fabrication of hydrogels is a frequent issue which is particularly concerning for biomedical or food packaging applications. In this study, novel antibacterial bionanocomposite films were obtained through a simple solvent casting technique without [...] Read more.

The use of toxic crosslinking agents and reagents in the fabrication of hydrogels is a frequent issue which is particularly concerning for biomedical or food packaging applications. In this study, novel antibacterial bionanocomposite films were obtained through a simple solvent casting technique without using any crosslinking substance. Films were made from a flexible and transparent whey protein matrix containing zinc oxide nanoparticles synthesised via a wet chemical precipitation route. The physicochemical and functional properties of the ZnO nanoparticles and of the composite films were characterised, and their antibacterial activity was tested against S. epidermidis and E. coli. The synthesised ZnO nanoparticles had an average size of about 30 nm and a specific surface area of 49.5 m²/g. The swelling ratio of the bionanocomposite films increased at basic pH, which is an appealing feature in relation to the absorption of chronic wound exudate. A n-ZnO concentration-dependent antibacterial effect was observed for composite films. In particular, marked antibacterial activity was observed against S. epidermidis. Overall, these findings suggest that this novel material can be a promising and sustainable alternative in the design of advanced solutions for wound dressing or food packaging. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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Review

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19 pages, 3422 KiB

Open AccessReview

Progress in Gelatin as Biomaterial for Tissue Engineering

by Izeia Lukin, Itsasne Erezuma, Lidia Maeso, Jon Zarate, Martin Federico Desimone, Taleb H. Al-Tel, Alireza Dolatshahi-Pirouz and Gorka Orive

Pharmaceutics 2022, 14(6), 1177; https://doi.org/10.3390/pharmaceutics14061177 - 31 May 2022

Cited by 70 | Viewed by 5268

Abstract

Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a [...] Read more.

Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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31 pages, 4115 KiB

Open AccessReview

Antibiotics-Free Compounds for Chronic Wound Healing

by David O. Oluwole, Lucy Coleman, William Buchanan, Tao Chen, Roberto M. La Ragione and Lian X. Liu

Pharmaceutics 2022, 14(5), 1021; https://doi.org/10.3390/pharmaceutics14051021 - 09 May 2022

Cited by 9 | Viewed by 3929

Abstract

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections [...] Read more.

The rapid rise in the health burden associated with chronic wounds is of great concern to policymakers, academia, and industry. This could be attributed to the devastating implications of this condition, and specifically, chronic wounds which have been linked to invasive microbial infections affecting patients’ quality of life. Unfortunately, antibiotics are not always helpful due to their poor penetration of bacterial biofilms and the emergence of antimicrobial resistance. Hence, there is an urgent need to explore antibiotics-free compounds/formulations with proven or potential antimicrobial, anti-inflammatory, antioxidant, and wound healing efficacy. The mechanism of antibiotics-free compounds is thought to include the disruption of the bacteria cell structure, preventing cell division, membrane porins, motility, and the formation of a biofilm. Furthermore, some of these compounds foster tissue regeneration by modulating growth factor expression. In this review article, the focus is placed on a number of non-antibiotic compounds possessing some of the aforementioned pharmacological and physiological activities. Specific interest is given to Aloevera, curcumin, cinnamaldehyde, polyhexanide, retinoids, ascorbate, tocochromanols, and chitosan. These compounds (when alone or in formulation with other biologically active molecules) could be a dependable alternative in the management or prevention of chronic wounds. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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46 pages, 8281 KiB

Open AccessReview

The 3D Bioprinted Scaffolds for Wound Healing

by Pablo Edmundo Antezana, Sofia Municoy, María Inés Álvarez-Echazú, Pablo Luis Santo-Orihuela, Paolo Nicolás Catalano, Taleb H. Al-Tel, Firoz Babu Kadumudi, Alireza Dolatshahi-Pirouz, Gorka Orive and Martin Federico Desimone

Pharmaceutics 2022, 14(2), 464; https://doi.org/10.3390/pharmaceutics14020464 - 21 Feb 2022

Cited by 39 | Viewed by 5197

Abstract

Skin tissue engineering and regeneration aim at repairing defective skin injuries and progress in wound healing. Until now, even though several developments are made in this field, it is still challenging to face the complexity of the tissue with current methods of fabrication. [...] Read more.

Skin tissue engineering and regeneration aim at repairing defective skin injuries and progress in wound healing. Until now, even though several developments are made in this field, it is still challenging to face the complexity of the tissue with current methods of fabrication. In this review, short, state-of-the-art on developments made in skin tissue engineering using 3D bioprinting as a new tool are described. The current bioprinting methods and a summary of bioink formulations, parameters, and properties are discussed. Finally, a representative number of examples and advances made in the field together with limitations and future needs are provided. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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21 pages, 2008 KiB

Open AccessReview

Polymer-Based Scaffolds Loaded with Aloe vera Extract for the Treatment of Wounds

by Sibusiso Alven, Vuyolwethu Khwaza, Opeoluwa O. Oyedeji and Blessing A. Aderibigbe

Pharmaceutics 2021, 13(7), 961; https://doi.org/10.3390/pharmaceutics13070961 - 26 Jun 2021

Cited by 27 | Viewed by 5186

Abstract

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial [...] Read more.

The treatment of wounds is one challenging biomedical field due to delayed wound healing common in chronic wounds. Several factors delay wound healing, including microbial infections, malnutrition, underlying physiological conditions, etc. Most of the currently used wound dressing materials suffer from poor antimicrobial properties, poor biodegradability and biocompatibility, and weak mechanical performance. Plant extracts, such as Aloe vera, have attracted significant attention in wound management because of their interesting biological properties. Aloe vera is composed of essential constituents beneficial for the wound healing process, such as amino acids, vitamins C and E, and zinc. Aloe vera influences numerous factors that are involved in wound healing and stimulates accelerated healing. This review reports the therapeutic outcomes of aloe vera extract-loaded polymer-based scaffolds in wound management. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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18 pages, 4182 KiB

Open AccessReview

Current Update of Collagen Nanomaterials—Fabrication, Characterisation and Its Applications: A Review

by Samantha Lo and Mh Busra Fauzi

Pharmaceutics 2021, 13(3), 316; https://doi.org/10.3390/pharmaceutics13030316 - 28 Feb 2021

Cited by 51 | Viewed by 6235

Abstract

Tissue engineering technology is a promising alternative approach for improvement in health management. Biomaterials play a major role, acting as a provisional bioscaffold for tissue repair and regeneration. Collagen a widely studied natural component largely present in the extracellular matrix (ECM) of the [...] Read more.

Tissue engineering technology is a promising alternative approach for improvement in health management. Biomaterials play a major role, acting as a provisional bioscaffold for tissue repair and regeneration. Collagen a widely studied natural component largely present in the extracellular matrix (ECM) of the human body. It provides mechanical stability with suitable elasticity and strength to various tissues, including skin, bone, tendon, cornea and others. Even though exogenous collagen is commonly used in bioscaffolds, largely in the medical and pharmaceutical fields, nano collagen is a relatively new material involved in nanotechnology with a plethora of unexplored potential. Nano collagen is a form of collagen reduced to a nanoparticulate size, which has its advantages over the common three-dimensional (3D) collagen design, primarily due to its nano-size contributing to a higher surface area-to-volume ratio, aiding in withstanding large loads with minimal tension. It can be produced through different approaches including the electrospinning technique to produce nano collagen fibres resembling natural ECM. Nano collagen can be applied in various medical fields involving bioscaffold insertion or fillers for wound healing improvement; skin, bone, vascular grafting, nerve tissue and articular cartilage regeneration as well as aiding in drug delivery and incorporation for cosmetic purposes. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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23 pages, 3358 KiB

Open AccessReview

Innovative Strategies in Tendon Tissue Engineering

by Eleonora Bianchi, Marco Ruggeri, Silvia Rossi, Barbara Vigani, Dalila Miele, Maria Cristina Bonferoni, Giuseppina Sandri and Franca Ferrari

Pharmaceutics 2021, 13(1), 89; https://doi.org/10.3390/pharmaceutics13010089 - 11 Jan 2021

Cited by 33 | Viewed by 6958

Abstract

The tendon is a highly aligned connective tissue that transmits force from muscle to bone. Each year, more than 32 million tendon injuries have been reported, in fact, tendinopathies represent at least 50% of all sports injuries, and their incidence rates have increased [...] Read more.

The tendon is a highly aligned connective tissue that transmits force from muscle to bone. Each year, more than 32 million tendon injuries have been reported, in fact, tendinopathies represent at least 50% of all sports injuries, and their incidence rates have increased in recent decades due to the aging population. Current clinical grafts used in tendon treatment are subject to several restrictions and there is a significant demand for alternative engineered tissue. For this reason, innovative strategies need to be explored. Tendon replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology and mechanical properties to stand the load. Moreover, to guide cell proliferation and growth, scaffolds should provide a fibrous network that mimics the collagen arrangement of the extracellular matrix in the tendons. This review focuses on tendon repair and regeneration. Particular attention has been devoted to the innovative approaches in tissue engineering. Advanced manufacturing techniques, such as electrospinning, soft lithography, and three-dimensional (3D) printing, have been described. Furthermore, biological augmentation has been considered, as an emerging strategy with great therapeutic potential. Full article

(This article belongs to the Special Issue Biopolymer Materials for Wound Healing)

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