Preparation, characterization, and in vitro evaluation of polymer-based wound dressings for the management of chronic wounds

Microbial infections are responsible for the retarded recovery process of chronic wounds. Polymer-based scaffolds possess features suitable for the treatment of chronic injuries. However, these scaffolds are commonly encapsulated with therapeutic agents to enhance their biological activities, including antibacterial efficacy. In this research, two types of polymer-based scaffolds were formulated and evaluated as effective formulations for the treatment of chronic wounds: sponges and topical gels. Sponges were formulated from cross-linking of gelatin and PEG. Ag nanoparticles and metronidazole were incorporated into the sponges to improve their antibacterial activity. Topical gels were loaded with essential oils and Ag nanoparticles and prepared from CMC and poloxamer. The prepared sponges and topical gels were evaluated using various analysis and characterization techniques. SEM/EDX, FTIR, and TGA were employed to characterize gelatin/PEG hybrid sponges followed by porosity, in vitro biodegradability, cytotoxicity, and antibacterial studies. FTIR, SEM/EDX, and TGA confirmed their physicochemical properties and successful fabrication of sponges loaded with metronidazole and Ag nanoparticles. The sponges were biodegradable, indicating their capability to induce skin regeneration. The drug release studies showed a rapid release of metronidazole 28.32-71.97 percent from the sponges over the first hour, followed by a sustained drug release. The Ag nanoparticles were released in a sustained manner, suggesting that these sponges can rapidly destroy bacteria and inhibit persisting bacterial infections as well as protect the lesion bed from further bacteria infections. The in vitro antibacterial studies of sponges displayed superior antibacterial activity against most of the Gram-negative and Gram-positive bacteria strains commonly found in chronic wound infections with a MIC value of 15.625 μg/mL. In vitro cytotoxicity experiments revealed excellent biocompatibility with a percent cell viability of more than 70 percent. The in vitro wound scratch healing assay exhibited that the sponges encapsulated with only metronidazole promoted high cell migration than the dual drug-loaded sponges and untreated cells, suggesting its potential to quicken the wound healing process. CMC/Poloxamer topical gels were also characterized by FTIR, followed by pH, viscosity, spreadability, cytotoxicity, and antibacterial studies. FTIR showed successful preparation of CMC/Poloxamer topical gels loaded with essential oils and Ag nanoparticles. The topical gels exhibited pH in the range of 5.20-6.68, spreadability between 5.4 and 5.9 cm, and viscosity ranged from 216 to 1200 cP at 50 rpm and 210–858 cP at 100 rpm. The in vitro drug release studies demonstrated that Ag nanoparticles were released from the topical gels in a sustained manner. Most formulated topical gels demonstrated superior antimicrobial efficacy against Gram-positive and Gram-negative bacteria strains than the blank gel and controls. The cytotoxicity analysis displayed more than 90.83 percent cell viability for the topical gels, revealing excellent biocompatibility. The outcomes revealed that the topical gels enriched with essential oils lavender and tea tree and Ag nanoparticles and sponges incorporated with metronidazole and Ag nanoparticles are potential wound dressing scaffolds that can be employed for the treatment of chronic infected injuries. The in vitro wound healing experiments showed that the HaCaT cells cultured with gels co-enriched with lavender oil and Ag nanoparticles possessed a higher rate of closure in comparison to the untreated cells for 96 hours.Thesis (PhD) -- Faculty of Science and Agriculture, 202

Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds

Diabetic wounds are severe injuries that are common in patients that suffer from diabetes. Most of the presently employed wound dressing scaffolds are inappropriate for treating diabetic wounds. Improper treatment of diabetic wounds usually results in amputations. The shortcomings that are related to the currently used wound dressings include poor antimicrobial properties, inability to provide moisture, weak mechanical features, poor biodegradability, and biocompatibility, etc. To overcome the poor mechanical properties, polymer-based wound dressings have been designed from the combination of biopolymers (natural polymers) (e.g., chitosan, alginate, cellulose, chitin, gelatin, etc.) and synthetic polymers (e.g., poly (vinyl alcohol), poly (lactic-co-glycolic acid), polylactide, poly-glycolic acid, polyurethanes, etc.) to produce effective hybrid scaffolds for wound management. The loading of bioactive agents or drugs into polymer-based wound dressings can result in improved therapeutic outcomes such as good antibacterial or antioxidant activity when used in the treatment of diabetic wounds. Based on the outstanding performance of polymer-based wound dressings on diabetic wounds in the pre-clinical experiments, the in vivo and in vitro therapeutic results of the wound dressing materials on the diabetic wound are hereby reviewed

Combination Therapy Strategies for the Treatment of Malaria

Malaria is a vector- and blood-borne infection that is responsible for a large number of deaths around the world. Most of the currently used antimalarial therapeutics suffer from drug resistance. The other limitations associated with the currently used antimalarial drugs are poor drug bioavailability, drug toxicity, and poor water solubility. Combination therapy is one of the best approaches that is currently used to treat malaria, whereby two or more therapeutic agents are combined. Different combination therapy strategies are used to overcome the aforementioned limitations. This review article reports two strategies of combination therapy; the incorporation of two or more antimalarials into polymer-based carriers and hybrid compounds designed by hybridization of two antimalarial pharmacophores

Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria

Cancer, malaria, and leishmaniasis remain the deadly diseases around the world although several strategies of treatment have been developed. However, most of the drugs used to treat the aforementioned diseases suffer from several pharmacological limitations such as poor pharmacokinetics, toxicity, drug resistance, poor bioavailability and water solubility. Artemisinin and its derivatives are antimalarial drugs. However, they also exhibit anticancer and antileishmanial activity. They have been evaluated as potential anticancer and antileishmanial drugs but their use is also limited by their poor water solubility and poor bioavailability. To overcome the aforementioned limitations associated with artemisinin and its derivatives used for the treatment of these diseases, they have been incorporated into nanoparticles. Several researchers incorporated this class of drugs into nanoparticles resulting in enhanced therapeutic outcomes. Their potential efficacy for the treatment of parasitic infections such as malaria and leishmaniasis and chronic diseases such as cancer has been reported. This review article will be focused on the nanoparticles formulations of artemisinin and derivatives for the treatment of cancer, malaria, and leishmaniasis and the biological outcomes (in vitro and in vivo)

The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo

Gellan Gum in Wound Dressing Scaffolds

Several factors, such as bacterial infections, underlying conditions, malnutrition, obesity, ageing, and smoking are the most common issues that cause a delayed process of wound healing. Developing wound dressings that promote an accelerated wound healing process and skin regeneration is crucial. The properties of wound dressings that make them suitable for the acceleration of the wound healing process include good antibacterial efficacy, excellent biocompatibility, and non-toxicity, the ability to provide a moist environment, stimulating cell migration and adhesion, and providing gaseous permeation. Biopolymers have demonstrated features appropriate for the development of effective wound dressing scaffolds. Gellan gum is one of the biopolymers that has attracted great attention in biomedical applications. The wound dressing materials fabricated from gellan gum possess outstanding properties when compared to traditional dressings, such as good biocompatibility, biodegradability, non-toxicity, renewability, and stable nature. This biopolymer has been broadly employed for the development of wound dressing scaffolds in different forms. This review discusses the physicochemical and biological properties of gellan gum-based scaffolds in the management of wounds

Polymer-Based Hydrogels Enriched with Essential Oils: A Promising Approach for the Treatment of Infected Wounds

Among the factors that delay the wound healing process in chronic wounds, bacterial infections are a common cause of acute wounds becoming chronic. Various therapeutic agents, such as antibiotics, metallic nanoparticles, and essential oils have been employed to treat infected wounds and also prevent the wounds from bacterial invasion. Essential oils are promising therapeutic agents with excellent wound healing, anti-inflammatory and antimicrobial activities, and good soothing effects. Some essential oils become chemically unstable when exposed to light, heat, oxygen, and moisture. The stability and biological activity of essential oil can be preserved via loading into hydrogels. The polymer-based hydrogels loaded with bioactive agents are regarded as ideal wound dressings with unique features, such as controlled and sustained drug release mechanisms, good antibacterial activity, non-toxicity, excellent cytocompatibility, good porosity, moderate water vapour transmission rate, etc. This review addresses the pre-clinical outcomes of hydrogels loaded with essential oils in the treatment of infected wounds

Collagen-Based Nanofibers for Skin Regeneration and Wound Dressing Applications

Skin regeneration after an injury is very vital, but this process can be impeded by several factors. Regenerative medicine is a developing biomedical field with the potential to decrease the need for an organ transplant. Wound management is challenging, particularly for chronic injuries, despite the availability of various types of wound dressing scaffolds in the market. Some of the wound dressings that are in clinical practice have various drawbacks such as poor antibacterial and antioxidant efficacy, poor mechanical properties, inability to absorb excess wound exudates, require frequent change of dressing and fails to offer a suitable moist environment to accelerate the wound healing process. Collagen is a biopolymer and a major constituent of the extracellular matrix (ECM), making it an interesting polymer for the development of wound dressings. Collagen-based nanofibers have demonstrated interesting properties that are advantageous both in the arena of skin regeneration and wound dressings, such as low antigenicity, good biocompatibility, hemostatic properties, capability to promote cellular proliferation and adhesion, and non-toxicity. Hence, this review will discuss the outcomes of collagen-based nanofibers reported from the series of preclinical trials of skin regeneration and wound healing

Polymer-Based Wound Dressing Materials Loaded with Bioactive Agents: Potential Materials for the Treatment of Diabetic Wounds

Diabetic wounds are severe injuries that are common in patients that suffer from diabetes. Most of the presently employed wound dressing scaffolds are inappropriate for treating diabetic wounds. Improper treatment of diabetic wounds usually results in amputations. The shortcomings that are related to the currently used wound dressings include poor antimicrobial properties, inability to provide moisture, weak mechanical features, poor biodegradability, and biocompatibility, etc. To overcome the poor mechanical properties, polymer-based wound dressings have been designed from the combination of biopolymers (natural polymers) (e.g., chitosan, alginate, cellulose, chitin, gelatin, etc.) and synthetic polymers (e.g., poly (vinyl alcohol), poly (lactic-co-glycolic acid), polylactide, poly-glycolic acid, polyurethanes, etc.) to produce effective hybrid scaffolds for wound management. The loading of bioactive agents or drugs into polymer-based wound dressings can result in improved therapeutic outcomes such as good antibacterial or antioxidant activity when used in the treatment of diabetic wounds. Based on the outstanding performance of polymer-based wound dressings on diabetic wounds in the pre-clinical experiments, the in vivo and in vitro therapeutic results of the wound dressing materials on the diabetic wound are hereby reviewed

Electrospun Nanofibers/Nanofibrous Scaffolds Loaded with Silver Nanoparticles as Effective Antibacterial Wound Dressing Materials

The treatment of wounds is expensive and challenging. Most of the available wound dressings are not effective and suffer from limitations such as poor antimicrobial activity, toxicity, inability to provide suitable moisture to the wound and poor mechanical performance. The use of inappropriate wound dressings can result in a delayed wound healing process. Nanosize range scaffolds have triggered great attention because of their attractive properties, which include their capability to deliver bioactive agents, high surface area, improved mechanical properties, mimic the extracellular matrix (ECM), and high porosity. Nanofibrous materials can be further encapsulated/loaded with metal-based nanoparticles to enhance their therapeutic outcomes in wound healing applications. The widely studied metal-based nanoparticles, silver nanoparticles exhibit good properties such as outstanding antibacterial activity, display antioxidant, and anti-inflammatory properties, support cell growth, making it an essential bioactive agent in wound dressings. This review article reports the biological (in vivo and in vitro) and mechanical outcomes of nanofibrous scaffolds loaded with silver nanoparticles on wound healing