International Journal of Biological Macromolecules, Sep 1, 2020
In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce it... more In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce its own cytokines, growth factors, and extracellular matrix, until the regenerated tissue gradually replaces the scaffold upon its degradation. However, the role of non-biodegradable scaffold remains unexplored. This study investigates the potential of a non-biodegradable bacterial nanocellulose/acrylic acid (BNC/AA) hydrogel to transfer human dermal fibroblasts (HDF) to the wound and the resulting healing effects of transferred HDF in athymic mice. Results demonstrated that the fabricated hydrogel successfully transferred >50% of HDF onto the wound site within 24 h, with evidence of HDF detected on day 7. The gene and protein study unveiled faster wound healing in the hydrogel with HDF group and characterized more mature newly formed skin microstructure on day 7, despite no visible differences. These findings give a new perspective regarding the role of non-biodegradable materials in skin tissue engineering, in the presence of exogenous cells, mainly at the molecular level.
International Journal of Pharmaceutics, Jun 1, 2016
The objective of this study was to investigate the in-vivo behavior of topically applied cationic... more The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
Hydrocortisone cream intended for atopic eczema often produces unwanted side effects after long-t... more Hydrocortisone cream intended for atopic eczema often produces unwanted side effects after long-term use. These side effects are essentially due to repeated percutaneous administration of the medication for skin dermatitis, as atopic eczema is a relapsing disorder. Hence, there is a need to develop a new hydrocortisone formulation that will deliver the drug more effectively and require a reduced dosing frequency; therefore, the side effects could be minimized. In this study, a hydroxypropyl methylcellulose (HPMC) lyogel system based on 80% organic and 20% aqueous solvents containing 1% hydrocortisone was formulated. The hydrocortisone lyogel physicochemical characteristics, rheological properties, stability profile, and in vitro Franz cell drug release properties, as well as the in vivo therapeutic efficacies and dermal irritancy in Balb/c mice were investigated. The HPMC lyogel appeared clear and soft and was easy to rub on the skin. The lyogel also showed a higher drug release profile compared with commercial hydrocortisone cream. Similar to the cream, HPMC lyogels exhibited pseudoplastic behavior. From the mouse model, the hydrocortisone lyogel showed higher inflammatory suppressive effects than the cream. However, it did not reduce the transepidermal water loss as effectively as the control did. The dermal irritancy testing revealed that the hydrocortisone lyogel caused minimal irritation. In conclusion, HPMC lyogel is a promising vehicle to deliver hydrocortisone topically, as it showed a higher drug release in vitro as well as enhanced therapeutic efficacy in resolving eczematous inflammatory reaction compared with commercial cream.
Bacterial infection and biofilm formation is a major concern in orthopaedic implants and bone rec... more Bacterial infection and biofilm formation is a major concern in orthopaedic implants and bone reconstructive surgery complications that may be addressed with localized drug delivery system. The potential use of a fabricated nanobiocomposite bone scaffold using alginate and nano cockle shell powder for drug release and antibacterial properties was investigated. Vancomycin loaded bone scaffolds were fabricated with 3 and 5 wt% vancomycin, respectively, while a non-drug loaded scaffold was used as controls. The mineralization of the scaffolds using simulated body fluid (SBF) as well as biofilm formation were evaluated using microscopic observations. Drug release study and antimicrobial activity of the eluent from each sampling period was tested for growth inhibition of Staphylococcus aureus and Staphylococcus epidermidis for a period of 21 days. Significant difference of cumulative amount of vancomycin eluted from scaffolds loaded with 5 wt% vancomycin compared to 3 wt% (p<0.05) were noted. Eluent from both groups showed inhibitory effect against bacterial strain tested for 21 days. The findings are further supported with histological observations of reduced biofilm formation by Staphylococcus epidermidis on surface of 5 wt% vancomycin loaded scaffolds compared to control scaffolds. Basic mineralization studies conducted showed no alteration in drug loaded scaffolds characteristics compared to control scaffolds. Findings from this study indicates antibacterial properties can be conferred to the fabricated bone scaffold with successful incorporation of vancomycin with potentials to be used for local drug delivery application.
Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good... more Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good reproducibility. For topical product assessment, the synthetic membrane should provide no diffusional resistance to drug diffusion. however, different synthetic membranes do show rate-limiting effects. The aims of this study were to validate and minimise errors that occur in Franz cell experiments, to examine the effect of different types of synthetic membrane on drug diffusion and to test the suitability of Franz cell experiments for drug release from a freeze-dried sodium alginate wafer and a sodium alginate gel. Franz cell experimental variables were validated using physical and visual tests, a plasticiser assay and incorporation of tonicity agents. The drug flux from a commercial gel was compared before and after validation. Thirteen types of synthetic membranes were screened using ibuprofen saturated solution. The impact of drug log P on flux was evaluated using ibuprofen (hydrophobic drug), riboflavin (hydrophilic drug) and four parabens of increasing Receptor Compound and
Polymerase chain reaction is an important tool in molecular biology. Although the principles of t... more Polymerase chain reaction is an important tool in molecular biology. Although the principles of the technique are relatively simple, amplifying complex or long DNA segments can be challenging. A variety of PCR additives are used to improve the performance and yield of difficult PCRs. Each PCR additive has unique properties and enhances PCR through a different mode of action. They are used to either improve PCR sensitivity, efficiency, and specificity, or mitigate the effects of PCR inhibitors. In this review, we categorise known PCR additives into four main groups. The first three groups comprise PCR additives with well-defined mechanisms, namely those that facilitate the amplification of GC-rich sequences, counteract the detrimental effects of PCR inhibitors, or alter PCR kinetics (nanomaterials). The fourth group is a loose mix of additives with unclear mechanisms of action. Then, we discuss how these additives may be used to tackle specific PCR-related challenges, particularly those associated with long-range PCR. We conclude the review with added insights into the use of PCR additives in enhancing the synthesis of complex and long DNA fragments.
Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable soci... more Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable social and economic burden globally. AD is primarily characterized by its chronic pattern and it can have important modifications in the quality of life of the patients and caretakers. One of the fastest-growing topics in translational medicine today is the exploration of new or repurposed functional biomaterials into drug delivery therapeutic applications. This area has gained a considerable amount of research which produced many innovative drug delivery systems for inflammatory skin diseases like AD. Chitosan, a polysaccharide, has attracted attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine, and has been considered a promising candidate for AD treatment due to its antimicrobial, antioxidative, and inflammatory response modulation properties. The current pharmacological treatment for AD involves prescribing topical corticosteroid and cal...
Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good... more Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good reproducibility. For topical product assessment, the synthetic membrane should provide no diffusional resistance to drug diffusion. however, different synthetic membranes do show rate-limiting effects. The aims of this study were to validate and minimise errors that occur in Franz cell experiments, to examine the effect of different types of synthetic membrane on drug diffusion and to test the suitability of Franz cell experiments for drug release from a freeze-dried sodium alginate wafer and a sodium alginate gel. Franz cell experimental variables were validated using physical and visual tests, a plasticiser assay and incorporation of tonicity agents. The drug flux from a commercial gel was compared before and after validation. Thirteen types of synthetic membranes were screened using ibuprofen saturated solution. The impact of drug log P on flux was evaluated using ibuprofen (hydrophobic drug), riboflavin (hydrophilic drug) and four parabens of increasing Receptor Compound and
Journal of Materials Research and Technology, 2020
Fatty acids derived from renewable sources have been shown to have promising antibacterial activi... more Fatty acids derived from renewable sources have been shown to have promising antibacterial activity. Palm glyceryl monocaprylate (GMCY), a medium chain fatty acids derived from palm kernel oil, was reported to have bactericidal effects. In this study, the potential application GMCY as antibacterial nanoformulation for the treatment of infected wounds was explored. First, the antibacterial activity of GMCY was tested against three common wound bacteria. Then, GMCY nanoemulsion was designed and optimised using response surface methodology (RSM) with particle size, zeta potential and polydispersity index as the response variables. In vivo infected wound healing study was conducted to examine the healing efficacy of the optimized GMCY nanoemulsion. It was showed that GMCY exhibited bactericidal properties against S. aureus and E. coli. At the nanoemulsion developmental stage, statistical analyses have demonstrated there was a direct correlation between GMCY concentration and the particle size and polydispersity index. Through the RSM models developed, an optimized nanoemulsion formulation that has the characteristics of 120 nm in particle size,-16.67 mV in zeta potential value and 0.1 polydispersity index. Electron microscopy observation on the bacteria morphology also demonstrated that increment in GMCY concentration as a direct effect on the disruption of the cell membrane integrity. From the animal study, it was found that the infected wounds in rats group treated with GMCY nanoemulsion was the most similar to normal healthy skin with no significant different. In conclusion, palm GMCY nanoemulsion can be explored as a plausible alternative antimicrobial formulation for the treatment of infected wounds.
Journal of Biomaterials Science, Polymer Edition, 2019
Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing w... more Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing wounds. It was found that the increased resistance of biofilms to antibiotics allows wound infections to persist chronically in spite of antibiotic therapy. In this study, the reduced form of graphene oxide (rGO) was explored as plausible antibiofilm agents. The rGO was synthesized via reducing the functional groups of GO. Then, rGO were characterized using zetasizer, X-ray photoelectron spectroscopy, UV-Vis spectroscopy and FESEM. The rGO were then formulated into sodium carboxymethyl cellulose (NaCMC) hydrogels to form rGO hydrogel and tested for antibiofilm activities in vitro using XTT test, and in vivo biofilm formation assay using nematodes C. elegans. Reduced GO hydrogel was successfully formed by reducing the functional groups of GO, and a reduction of up to 95% of functional groups was confirmed with X-ray photoelectron spectroscopy analysis. XTT tests confirmed that rGO hydrogels reduced biofilm formation by S. aureus (81-84%) and P. aeruginosa (50-62%). Fluorescence intensity also confirmed that rGO hydrogel can inhibit biofilm bacteria in C. elegans experiments. This study implied that rGO hydrogel is an effective antibiofilm agent for infected wounds.
International journal of biological macromolecules, Jan 4, 2017
Natural polymer-based hydrogel films have great potential for biomedical applications and are goo... more Natural polymer-based hydrogel films have great potential for biomedical applications and are good candidates for wound dressings. In this study, we aimed to develop simvastatin-loaded crosslinked alginate-pectin hydrogel films by ionic crosslinking to improve the mechanical characteristics, wound fluid uptake and drug release behavior. Alginate-pectin hydrocolloid films were chemically crosslinked by immersing in different concentrations of CaCl2 (0.5-3% w/v) for 2-20min. The degree of crosslinking was influenced by both contact time and CaCl2 concentration. The optimized conditions for crosslinking were 0.5% and 1% (CaCl2) for 2min. The optimized hydrogel films were then characterized for their physical, mechanical, morphological, thermal, in vitro drug release, and cytocompatibility profiles. Crosslinking improved the mechanical profile and wound fluid uptake capacity of dressings. The hydrogel films were able to maintain their physical integrity during use, and the best results ...
Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular... more Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular structures, leading to restoration of the skin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s barrier function, re-establishment of tissue integrity, and maintenance of the internal homeostasis. Curcumin (CUR) and its analogs have gained widespread recognition due to their remarkable anti-inflammatory, anti-infective, anticancer, immunomodulatory, antioxidant, and wound healing activities. However, their pharmaceutical significance is limited due to inherent hydrophobic nature, poor water solubility, low bioavailability, chemical instability, rapid metabolism and short half-life. Owing to their pharmaceutical limitations, newer strategies have been attempted in recent years aiming to mitigate problems related to the effective delivery of curcumanoids and to improve their wound healing potential. These advanced strategies include nanovesicles, polymeric micelles, conventional liposomes and hyalurosomes, nanocomposite hydrogels, electrospun nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, nanodispersion, and polymeric nanoparticles (NPs). The superior wound healing activities achieved after nanoencapsulation of the CUR are attributed to its target-specific delivery, longer retention at the target site, avoiding premature degradation of the encapsulated cargo and the therapeutic superiority of the advanced delivery systems over the conventional delivery. We have critically reviewed the literature and summarize the convincing evidence which explore the pharmaceutical significance and therapeutic feasibility of the advanced delivery systems in improving wound healing activities of the CUR and its analogs.
The objective of this study was to investigate the in-vivo behavior of topically applied cationic... more The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the ... more Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD 50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter R , Mexameter R , and as observed visually. Moreover, no-observedadverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.
The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and... more The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and to investigate its potential as slow-release wound healing vehicle. The bilayer is composed of an upper layer impregnated with model drug (ibuprofen) and a drug-free lower layer, which acted as a rate-controlling membrane. The thickness uniformity, solvent loss, moisture vapour transmission rate (MVTR), hydration rate, morphology, rheology, mechanical properties, in vitro drug release and in vivo wound healing profiles were investigated. A smooth bilayer film with two homogenous distinct layers was produced. The characterisation results showed that bilayer has superior mechanical and rheological properties than the single layer films. The bilayers also showed low MVTR, slower hydration rate and lower drug flux in vitro compared to single layer inferring that bilayer may be useful for treating low suppurating wounds and suitable for slow release application on wound surfaces. The bilayers also provided a significant higher healing rate in vivo, with well-formed epidermis with faster granulation tissue formation when compared to the controls. In conclusions, a novel alginate-based bilayer hydrocolloid film was developed and results suggested that they can be exploited as slow-release wound dressings.
Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the ... more Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil ‚ , are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.
Hyperpigmentation affects people globally with negative psychological impacts. Piper betle L. lea... more Hyperpigmentation affects people globally with negative psychological impacts. Piper betle L. leaf (PBL) extract has many benefits including skin lightening which may reduce hyperpigmentation. The objective of this study was to develop an effective skin-lightening cream containing PBL with ideal characteristics. A formulation of base cream and PBL cream was prepared and characterized by centrifugation, particle size and zeta potential analysis, rheological profile studies and physical properties’ observation. In vivo studies on 30 human subjects tested the effects of base and PBL cream on skin-lightening, hydration, trans-epidermal water loss (TEWL) and elasticity through weekly tests 4 weeks in duration. Base and PBL creams had a non-Newtonian property with acceptable color, odor, texture, zeta potential, particle size and showed no phase separation. The in vivo study indicated a significant reduction in melanin content and an improvement in skin tone for PBL cream but not in base ...
International Journal of Biological Macromolecules, Sep 1, 2020
In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce it... more In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce its own cytokines, growth factors, and extracellular matrix, until the regenerated tissue gradually replaces the scaffold upon its degradation. However, the role of non-biodegradable scaffold remains unexplored. This study investigates the potential of a non-biodegradable bacterial nanocellulose/acrylic acid (BNC/AA) hydrogel to transfer human dermal fibroblasts (HDF) to the wound and the resulting healing effects of transferred HDF in athymic mice. Results demonstrated that the fabricated hydrogel successfully transferred >50% of HDF onto the wound site within 24 h, with evidence of HDF detected on day 7. The gene and protein study unveiled faster wound healing in the hydrogel with HDF group and characterized more mature newly formed skin microstructure on day 7, despite no visible differences. These findings give a new perspective regarding the role of non-biodegradable materials in skin tissue engineering, in the presence of exogenous cells, mainly at the molecular level.
International Journal of Pharmaceutics, Jun 1, 2016
The objective of this study was to investigate the in-vivo behavior of topically applied cationic... more The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
Hydrocortisone cream intended for atopic eczema often produces unwanted side effects after long-t... more Hydrocortisone cream intended for atopic eczema often produces unwanted side effects after long-term use. These side effects are essentially due to repeated percutaneous administration of the medication for skin dermatitis, as atopic eczema is a relapsing disorder. Hence, there is a need to develop a new hydrocortisone formulation that will deliver the drug more effectively and require a reduced dosing frequency; therefore, the side effects could be minimized. In this study, a hydroxypropyl methylcellulose (HPMC) lyogel system based on 80% organic and 20% aqueous solvents containing 1% hydrocortisone was formulated. The hydrocortisone lyogel physicochemical characteristics, rheological properties, stability profile, and in vitro Franz cell drug release properties, as well as the in vivo therapeutic efficacies and dermal irritancy in Balb/c mice were investigated. The HPMC lyogel appeared clear and soft and was easy to rub on the skin. The lyogel also showed a higher drug release profile compared with commercial hydrocortisone cream. Similar to the cream, HPMC lyogels exhibited pseudoplastic behavior. From the mouse model, the hydrocortisone lyogel showed higher inflammatory suppressive effects than the cream. However, it did not reduce the transepidermal water loss as effectively as the control did. The dermal irritancy testing revealed that the hydrocortisone lyogel caused minimal irritation. In conclusion, HPMC lyogel is a promising vehicle to deliver hydrocortisone topically, as it showed a higher drug release in vitro as well as enhanced therapeutic efficacy in resolving eczematous inflammatory reaction compared with commercial cream.
Bacterial infection and biofilm formation is a major concern in orthopaedic implants and bone rec... more Bacterial infection and biofilm formation is a major concern in orthopaedic implants and bone reconstructive surgery complications that may be addressed with localized drug delivery system. The potential use of a fabricated nanobiocomposite bone scaffold using alginate and nano cockle shell powder for drug release and antibacterial properties was investigated. Vancomycin loaded bone scaffolds were fabricated with 3 and 5 wt% vancomycin, respectively, while a non-drug loaded scaffold was used as controls. The mineralization of the scaffolds using simulated body fluid (SBF) as well as biofilm formation were evaluated using microscopic observations. Drug release study and antimicrobial activity of the eluent from each sampling period was tested for growth inhibition of Staphylococcus aureus and Staphylococcus epidermidis for a period of 21 days. Significant difference of cumulative amount of vancomycin eluted from scaffolds loaded with 5 wt% vancomycin compared to 3 wt% (p<0.05) were noted. Eluent from both groups showed inhibitory effect against bacterial strain tested for 21 days. The findings are further supported with histological observations of reduced biofilm formation by Staphylococcus epidermidis on surface of 5 wt% vancomycin loaded scaffolds compared to control scaffolds. Basic mineralization studies conducted showed no alteration in drug loaded scaffolds characteristics compared to control scaffolds. Findings from this study indicates antibacterial properties can be conferred to the fabricated bone scaffold with successful incorporation of vancomycin with potentials to be used for local drug delivery application.
Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good... more Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good reproducibility. For topical product assessment, the synthetic membrane should provide no diffusional resistance to drug diffusion. however, different synthetic membranes do show rate-limiting effects. The aims of this study were to validate and minimise errors that occur in Franz cell experiments, to examine the effect of different types of synthetic membrane on drug diffusion and to test the suitability of Franz cell experiments for drug release from a freeze-dried sodium alginate wafer and a sodium alginate gel. Franz cell experimental variables were validated using physical and visual tests, a plasticiser assay and incorporation of tonicity agents. The drug flux from a commercial gel was compared before and after validation. Thirteen types of synthetic membranes were screened using ibuprofen saturated solution. The impact of drug log P on flux was evaluated using ibuprofen (hydrophobic drug), riboflavin (hydrophilic drug) and four parabens of increasing Receptor Compound and
Polymerase chain reaction is an important tool in molecular biology. Although the principles of t... more Polymerase chain reaction is an important tool in molecular biology. Although the principles of the technique are relatively simple, amplifying complex or long DNA segments can be challenging. A variety of PCR additives are used to improve the performance and yield of difficult PCRs. Each PCR additive has unique properties and enhances PCR through a different mode of action. They are used to either improve PCR sensitivity, efficiency, and specificity, or mitigate the effects of PCR inhibitors. In this review, we categorise known PCR additives into four main groups. The first three groups comprise PCR additives with well-defined mechanisms, namely those that facilitate the amplification of GC-rich sequences, counteract the detrimental effects of PCR inhibitors, or alter PCR kinetics (nanomaterials). The fourth group is a loose mix of additives with unclear mechanisms of action. Then, we discuss how these additives may be used to tackle specific PCR-related challenges, particularly those associated with long-range PCR. We conclude the review with added insights into the use of PCR additives in enhancing the synthesis of complex and long DNA fragments.
Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable soci... more Atopic dermatitis (AD) is a complex, relapsing inflammatory skin disease with a considerable social and economic burden globally. AD is primarily characterized by its chronic pattern and it can have important modifications in the quality of life of the patients and caretakers. One of the fastest-growing topics in translational medicine today is the exploration of new or repurposed functional biomaterials into drug delivery therapeutic applications. This area has gained a considerable amount of research which produced many innovative drug delivery systems for inflammatory skin diseases like AD. Chitosan, a polysaccharide, has attracted attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine, and has been considered a promising candidate for AD treatment due to its antimicrobial, antioxidative, and inflammatory response modulation properties. The current pharmacological treatment for AD involves prescribing topical corticosteroid and cal...
Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good... more Franz diffusion cells employ synthetic membranes because of membrane simplicity and supposed good reproducibility. For topical product assessment, the synthetic membrane should provide no diffusional resistance to drug diffusion. however, different synthetic membranes do show rate-limiting effects. The aims of this study were to validate and minimise errors that occur in Franz cell experiments, to examine the effect of different types of synthetic membrane on drug diffusion and to test the suitability of Franz cell experiments for drug release from a freeze-dried sodium alginate wafer and a sodium alginate gel. Franz cell experimental variables were validated using physical and visual tests, a plasticiser assay and incorporation of tonicity agents. The drug flux from a commercial gel was compared before and after validation. Thirteen types of synthetic membranes were screened using ibuprofen saturated solution. The impact of drug log P on flux was evaluated using ibuprofen (hydrophobic drug), riboflavin (hydrophilic drug) and four parabens of increasing Receptor Compound and
Journal of Materials Research and Technology, 2020
Fatty acids derived from renewable sources have been shown to have promising antibacterial activi... more Fatty acids derived from renewable sources have been shown to have promising antibacterial activity. Palm glyceryl monocaprylate (GMCY), a medium chain fatty acids derived from palm kernel oil, was reported to have bactericidal effects. In this study, the potential application GMCY as antibacterial nanoformulation for the treatment of infected wounds was explored. First, the antibacterial activity of GMCY was tested against three common wound bacteria. Then, GMCY nanoemulsion was designed and optimised using response surface methodology (RSM) with particle size, zeta potential and polydispersity index as the response variables. In vivo infected wound healing study was conducted to examine the healing efficacy of the optimized GMCY nanoemulsion. It was showed that GMCY exhibited bactericidal properties against S. aureus and E. coli. At the nanoemulsion developmental stage, statistical analyses have demonstrated there was a direct correlation between GMCY concentration and the particle size and polydispersity index. Through the RSM models developed, an optimized nanoemulsion formulation that has the characteristics of 120 nm in particle size,-16.67 mV in zeta potential value and 0.1 polydispersity index. Electron microscopy observation on the bacteria morphology also demonstrated that increment in GMCY concentration as a direct effect on the disruption of the cell membrane integrity. From the animal study, it was found that the infected wounds in rats group treated with GMCY nanoemulsion was the most similar to normal healthy skin with no significant different. In conclusion, palm GMCY nanoemulsion can be explored as a plausible alternative antimicrobial formulation for the treatment of infected wounds.
Journal of Biomaterials Science, Polymer Edition, 2019
Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing w... more Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing wounds. It was found that the increased resistance of biofilms to antibiotics allows wound infections to persist chronically in spite of antibiotic therapy. In this study, the reduced form of graphene oxide (rGO) was explored as plausible antibiofilm agents. The rGO was synthesized via reducing the functional groups of GO. Then, rGO were characterized using zetasizer, X-ray photoelectron spectroscopy, UV-Vis spectroscopy and FESEM. The rGO were then formulated into sodium carboxymethyl cellulose (NaCMC) hydrogels to form rGO hydrogel and tested for antibiofilm activities in vitro using XTT test, and in vivo biofilm formation assay using nematodes C. elegans. Reduced GO hydrogel was successfully formed by reducing the functional groups of GO, and a reduction of up to 95% of functional groups was confirmed with X-ray photoelectron spectroscopy analysis. XTT tests confirmed that rGO hydrogels reduced biofilm formation by S. aureus (81-84%) and P. aeruginosa (50-62%). Fluorescence intensity also confirmed that rGO hydrogel can inhibit biofilm bacteria in C. elegans experiments. This study implied that rGO hydrogel is an effective antibiofilm agent for infected wounds.
International journal of biological macromolecules, Jan 4, 2017
Natural polymer-based hydrogel films have great potential for biomedical applications and are goo... more Natural polymer-based hydrogel films have great potential for biomedical applications and are good candidates for wound dressings. In this study, we aimed to develop simvastatin-loaded crosslinked alginate-pectin hydrogel films by ionic crosslinking to improve the mechanical characteristics, wound fluid uptake and drug release behavior. Alginate-pectin hydrocolloid films were chemically crosslinked by immersing in different concentrations of CaCl2 (0.5-3% w/v) for 2-20min. The degree of crosslinking was influenced by both contact time and CaCl2 concentration. The optimized conditions for crosslinking were 0.5% and 1% (CaCl2) for 2min. The optimized hydrogel films were then characterized for their physical, mechanical, morphological, thermal, in vitro drug release, and cytocompatibility profiles. Crosslinking improved the mechanical profile and wound fluid uptake capacity of dressings. The hydrogel films were able to maintain their physical integrity during use, and the best results ...
Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular... more Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular structures, leading to restoration of the skin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s barrier function, re-establishment of tissue integrity, and maintenance of the internal homeostasis. Curcumin (CUR) and its analogs have gained widespread recognition due to their remarkable anti-inflammatory, anti-infective, anticancer, immunomodulatory, antioxidant, and wound healing activities. However, their pharmaceutical significance is limited due to inherent hydrophobic nature, poor water solubility, low bioavailability, chemical instability, rapid metabolism and short half-life. Owing to their pharmaceutical limitations, newer strategies have been attempted in recent years aiming to mitigate problems related to the effective delivery of curcumanoids and to improve their wound healing potential. These advanced strategies include nanovesicles, polymeric micelles, conventional liposomes and hyalurosomes, nanocomposite hydrogels, electrospun nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, nanodispersion, and polymeric nanoparticles (NPs). The superior wound healing activities achieved after nanoencapsulation of the CUR are attributed to its target-specific delivery, longer retention at the target site, avoiding premature degradation of the encapsulated cargo and the therapeutic superiority of the advanced delivery systems over the conventional delivery. We have critically reviewed the literature and summarize the convincing evidence which explore the pharmaceutical significance and therapeutic feasibility of the advanced delivery systems in improving wound healing activities of the CUR and its analogs.
The objective of this study was to investigate the in-vivo behavior of topically applied cationic... more The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.
Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the ... more Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD 50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter R , Mexameter R , and as observed visually. Moreover, no-observedadverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.
The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and... more The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and to investigate its potential as slow-release wound healing vehicle. The bilayer is composed of an upper layer impregnated with model drug (ibuprofen) and a drug-free lower layer, which acted as a rate-controlling membrane. The thickness uniformity, solvent loss, moisture vapour transmission rate (MVTR), hydration rate, morphology, rheology, mechanical properties, in vitro drug release and in vivo wound healing profiles were investigated. A smooth bilayer film with two homogenous distinct layers was produced. The characterisation results showed that bilayer has superior mechanical and rheological properties than the single layer films. The bilayers also showed low MVTR, slower hydration rate and lower drug flux in vitro compared to single layer inferring that bilayer may be useful for treating low suppurating wounds and suitable for slow release application on wound surfaces. The bilayers also provided a significant higher healing rate in vivo, with well-formed epidermis with faster granulation tissue formation when compared to the controls. In conclusions, a novel alginate-based bilayer hydrocolloid film was developed and results suggested that they can be exploited as slow-release wound dressings.
Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the ... more Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil ‚ , are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.
Hyperpigmentation affects people globally with negative psychological impacts. Piper betle L. lea... more Hyperpigmentation affects people globally with negative psychological impacts. Piper betle L. leaf (PBL) extract has many benefits including skin lightening which may reduce hyperpigmentation. The objective of this study was to develop an effective skin-lightening cream containing PBL with ideal characteristics. A formulation of base cream and PBL cream was prepared and characterized by centrifugation, particle size and zeta potential analysis, rheological profile studies and physical properties’ observation. In vivo studies on 30 human subjects tested the effects of base and PBL cream on skin-lightening, hydration, trans-epidermal water loss (TEWL) and elasticity through weekly tests 4 weeks in duration. Base and PBL creams had a non-Newtonian property with acceptable color, odor, texture, zeta potential, particle size and showed no phase separation. The in vivo study indicated a significant reduction in melanin content and an improvement in skin tone for PBL cream but not in base ...
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