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1.
AAPS PharmSciTech ; 25(5): 110, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740721

ABSTRACT

Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.


Subject(s)
Anti-Bacterial Agents , Bandages , Chitosan , Escherichia coli , Hydrogels , Microspheres , Pseudomonas aeruginosa , Staphylococcus aureus , Chitosan/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Staphylococcus aureus/drug effects , Humans , Pseudomonas aeruginosa/drug effects , Escherichia coli/drug effects , Wound Healing/drug effects , Wound Infection/drug therapy , Wound Infection/microbiology , Wound Infection/prevention & control , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/administration & dosage , Cathelicidins , Microbial Sensitivity Tests/methods , Bacterial Toxins , Drug Liberation , Cell Movement/drug effects , Carbon/chemistry , Biofilms/drug effects
2.
Curr Med Res Opin ; 40(5): 753-763, 2024 May.
Article in English | MEDLINE | ID: mdl-38625386

ABSTRACT

Atopic dermatitis (AD) has become a common childhood disease that affects a large number of children worldwide and has become a chronic skin disease that causes huge economical and psychological damage to the whole family. Despite the use of steroids, immunosuppressants, and various topical preparation, the prognosis is still poor. Hence, this review aimed to explore the potential of using essential oils (EO) as an active ingredient in managing AD. The review was completed by using Pubmed, Scopus, and Medline to search for relevant articles that study the pathophysiology of AD, the properties of EO, the use of EO in managing AD, and the suitable advanced formulation to incorporate EO. From the review conducted, it was concluded that EO have huge potential in managing AD and can be used as complimentary therapeutic agents in AD treatment. Scientists and industries should venture into commercializing more topical products with EO to help manage AD more effectively.


Subject(s)
Dermatitis, Atopic , Oils, Volatile , Dermatitis, Atopic/drug therapy , Humans , Oils, Volatile/therapeutic use , Oils, Volatile/administration & dosage , Child
3.
Int J Nanomedicine ; 19: 3697-3714, 2024.
Article in English | MEDLINE | ID: mdl-38681091

ABSTRACT

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections. Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied. Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy. Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.


Subject(s)
Alginates , Anti-Bacterial Agents , Biofilms , Gold , Nanotubes , Polyethylenes , Quaternary Ammonium Compounds , Staphylococcus aureus , Biofilms/drug effects , Gold/chemistry , Gold/pharmacology , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Alginates/chemistry , Alginates/pharmacology , Nanotubes/chemistry , Animals , Mice , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyethylenes/chemistry , Polyethylenes/pharmacology , Staphylococcal Infections/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/physiology , Cell Line , Microbial Sensitivity Tests , Metal Nanoparticles/chemistry
4.
Drug Deliv Transl Res ; 13(5): 1436-1455, 2023 05.
Article in English | MEDLINE | ID: mdl-36808298

ABSTRACT

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 calcineurin inhibitors. However, the adverse reactions associated with the long-term usage of these drugs such as itching, burning, or stinging sensation are also well documented. Innovative formulation strategies, including the use of micro- and nanoparticulate systems, biopolymer hydrogel composites, nanofibers, and textile fabrication are being extensively researched with an aim to produce a safe and effective delivery system for AD treatment with minimal side effects. This review outlines the recent development of various chitosan-based drug delivery systems for the treatment of AD published in the past 10 years (2012-2022). These chitosan-based delivery systems include hydrogels, films, micro-, and nanoparticulate systems as well as chitosan textile. The global patent trends on chitosan-based formulations for the AD are also discussed.


Subject(s)
Chitosan , Dermatitis, Atopic , Humans , Dermatitis, Atopic/drug therapy , Chitosan/therapeutic use , Quality of Life , Skin , Drug Delivery Systems
5.
Biochimie ; 197: 130-143, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35231536

ABSTRACT

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.


Subject(s)
DNA , Regulatory Sequences, Nucleic Acid , DNA/genetics , GC Rich Sequence , Polymerase Chain Reaction/methods
6.
Polymers (Basel) ; 13(24)2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34960943

ABSTRACT

The clinical use of platelet lysate (PL) in the treatment of wounds is limited by its rapid degradation by proteases at the tissue site. This research aims to develop a chitosan (CS) and kenaf nanocrystalline cellulose (NCC) hydrogel composite, which intend to stabilize PL and control its release onto the wound site for prolonged action. NCC was synthesized from raw kenaf bast fibers and incorporated into the CS hydrogel. The physicochemical properties, in vitro cytocompatibility, cell proliferation, wound scratch assay, PL release, and CS stabilizing effect of the hydrogel composites were analyzed. The study of swelling ratio (>1000%) and moisture loss (60-90%) showed the excellent water retention capacity of the CS-NCC-PL hydrogels as compared with the commercial product. In vitro release PL study (flux = 0.165 mg/cm2/h) indicated that NCC act as a nanofiller and provided the sustained release of PL compared with the CS hydrogel alone. The CS also showed the protective effect of growth factor (GF) present in PL, thereby promoting fast wound healing via the formulation. The CS-NCC hydrogels also augmented fibroblast proliferation in vitro and enhanced wound closures over 72 h. This study provides a new insight on CS with renewable source kenaf NCC as a nanofiller as a potential autologous PL wound therapy.

7.
Nanomaterials (Basel) ; 11(10)2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34685010

ABSTRACT

Nano-hydroxyapatite (nHA) has been widely used as an orthopedic biomaterial and vehicle for drug delivery owing to its chemical and structural similarity to bone minerals. Several studies have demonstrated that nHA based biomaterials have a potential effect for bone regeneration with very minimal to no toxicity or inflammatory response. This systematic review aims to provide an appraisal of the effectiveness of nHA as a delivery system for bone regeneration and whether the conjugation of proteins, antibiotics, or other bioactive molecules to the nHA further enhances osteogenesis in vivo. Out of 282 articles obtained from the literature search, only 14 articles met the inclusion criteria for this review. These studies showed that nHA was able to induce bone regeneration in various animal models with large or critical-sized bone defects, open fracture, or methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. The conjugations of drugs or bioactive molecules such as bone-morphogenetic protein-2 (BMP-2), vancomycin, calcitriol, dexamethasone, and cisplatin were able to enhance the osteogenic property of nHA. Thus, nHA is a promising delivery system for a variety of compounds in promoting bone regeneration in vivo.

8.
Pharmaceutics ; 13(8)2021 Aug 18.
Article in English | MEDLINE | ID: mdl-34452250

ABSTRACT

Andrographolide (AG) is an active compound isolated from Andrographis paniculata (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. To overcome the problem, an AG-loaded nanoemulsion (AG-NE) was formulated and prepared using a microfluidization technique. This study aimed to investigate the effect of pressure and the number of homogenization cycles (factors) on droplet size, polydispersity index and zeta potential of AG-NE (responses) and to determine the effect of AG-NE on skin cancer cells and UVB irradiation-induced skin disorders in rats. Relationships between factors versus responses obtained from the face-centered central composite design were described by quadratic models. The optimum value of parameters for the production of optimized AG-NE (Op-AG-NE) were 20,000 psi of pressure and 5 homogenization cycles. Op-AG-NE showed promising cytotoxicity effects on the human malignant melanoma- (A375 cells) and non-melanoma cells (A-431 cells) via apoptosis induction with a high selectivity index and also inhibited intracellular tyrosinase activity in the A375 cells. Op-AG-NE could reduce melanin index and healed UVB irradiation exposed skin. Op-AG-NE thus had potential for treatment of skin cancers and skin disorders from exposure to UVB radiation.

9.
Curr Pharm Teach Learn ; 13(5): 479-491, 2021 05.
Article in English | MEDLINE | ID: mdl-33795099

ABSTRACT

INTRODUCTION: The incorporation of serious games in higher education has shown improvement in student engagement and motivation to learn. Research that explores local pharmacy student preferences of gamification aspects of serious games is scarce. Therefore, this study was conducted to investigate local pharmacy student experience, preference, and perceptions of gaming and game-based learning. METHODS: A cross-sectional study was conducted by distributing self-administered questionnaires among pharmacy students in Malaysia. Descriptive statistics, the Mann-Whitney test, the Kruskal-Wallis test, and the Spearman's correlation test were used for analysis. RESULTS: A total of 328 pharmacy students enrolled in this study, and 84.1% (n = 276) had video game experience. Students usually played video games using mobile phones (n = 231, 70%). Pharmacy students showed positive perceptions regarding serious games with a mean score of 3.69. However, limited awareness and knowledge of serious games was observed among pharmacy students. The most preferred game genres were role-playing and strategy (n = 174, 53%). Pharmacy students also preferred playing a cooperative game style (n = 113, 34.5%) with scores as a reward system (n = 204, 62.6%). Over three quarters (n = 292, 89.3%) wanted to see the results of the assessment after the game. CONCLUSIONS: This research provided information on serious games preferences of local pharmacy students. Further study should evaluate the acceptance and effectiveness of the implementation of serious games among pharmacy students in Malaysia.


Subject(s)
Students, Pharmacy , Video Games , Cross-Sectional Studies , Humans , Motivation , Perception
10.
Int J Biol Macromol ; 171: 308-319, 2021 Feb 28.
Article in English | MEDLINE | ID: mdl-33421467

ABSTRACT

Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p < 0.05) higher than the control after 21-day treatment and wound closure was ~99% without any adverse systemic reactions. Histological analysis qualitatively revealed an enhanced re-epithelialization and collagen deposition. Moreover, results also showed an improved rate of collagen synthesis and angiogenesis in the group treated with the hydrogel film loaded with Simvastatin. Thus, the present study demonstrated that developed film holds great potential for the acceleration of diabetic wound healing by its pro-angiogenic effect, faster re-epithelialization and increased collagen deposition.


Subject(s)
Alginates/administration & dosage , Biological Dressings , Diabetes Mellitus, Experimental/complications , Hydrogels , Pectins/administration & dosage , Simvastatin/administration & dosage , Wound Healing/drug effects , Alginates/chemistry , Animals , Collagen/biosynthesis , Drug Evaluation, Preclinical , Drug Repositioning , Hydrogels/administration & dosage , Hydrogels/pharmacology , Hydrogels/therapeutic use , Hydroxyproline/analysis , Male , Materials Testing , Neovascularization, Physiologic/drug effects , Pectins/chemistry , Random Allocation , Rats , Rats, Wistar , Re-Epithelialization/drug effects , Simvastatin/pharmacology , Simvastatin/therapeutic use , Skin/injuries , Vascular Endothelial Growth Factor A/biosynthesis
11.
Int J Nanomedicine ; 15: 9961-9974, 2020.
Article in English | MEDLINE | ID: mdl-33324057

ABSTRACT

Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health. However, the poor bioavailability of vitamin E, especially tocotrienols, remains a great limitation for clinical applications. Recently, nanoformulations that include nanovesicles, solid-lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and polymeric nanoparticles have shown promising outcomes in improving the efficacy and bioavailability of vitamin E. This review focuses on the pharmacological properties and pharmacokinetics of vitamin E and current advances in vitamin E nanoformulations for future clinical applications. The limitations and future recommendations are also discussed in this review.


Subject(s)
Nanostructures/chemistry , Vitamin E/pharmacology , Vitamin E/pharmacokinetics , Biological Availability , Drug Compounding , Humans , Vitamin E/chemistry
12.
Polymers (Basel) ; 12(11)2020 Nov 06.
Article in English | MEDLINE | ID: mdl-33171959

ABSTRACT

Improved physicochemical properties of chitosan-curcumin nanoparticulate carriers using microwave technology for skin burn wound application are reported. The microwave modified low molecular weight chitosan variant was used for nanoparticle formulation by ionic gelation method nanoparticles analyzed for their physicochemical properties. The antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa cultures, cytotoxicity and cell migration using human dermal fibroblasts-an adult cell line-were studied. The microwave modified chitosan variant had significantly reduced molecular weight, increased degree of deacetylation and decreased specific viscosity. The nanoparticles were nano-sized with high positive charge and good dispersibility with entrapment efficiency and drug content in between 99% and 100%, demonstrating almost no drug loss. Drug release was found to be sustained following Fickian the diffusion mechanism for drug release with higher cumulative drug release observed for formulation (F)2. The microwave treatment does not render a destructive effect on the chitosan molecule with the drug embedded in the core of nanoparticles. The optimized formulation precluded selected bacterial strain colonization, exerted no cytotoxic effect, and promoted cell migration within 24 h post application in comparison to blank and/or control application. Microwave modified low molecular weight chitosan-curcumin nanoparticles hold potential in delivery of curcumin into the skin to effectively treat skin manifestations.

13.
Int J Biol Macromol ; 159: 497-509, 2020 Sep 15.
Article in English | MEDLINE | ID: mdl-32387606

ABSTRACT

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.


Subject(s)
Bacteria/chemistry , Cellulose/chemistry , Fibroblasts/transplantation , Nanogels/chemistry , Wound Healing , Biomarkers , Cell Survival , Cells, Cultured , Extracellular Matrix , Gene Expression Profiling , Re-Epithelialization , Skin/cytology , Skin/metabolism , Tissue Engineering
14.
Biomed Res Int ; 2020: 4730858, 2020.
Article in English | MEDLINE | ID: mdl-32382552

ABSTRACT

Chronic wounds represent serious globally health care and economic issues especially for patients with hyperglycemic condition. Wound dressings have a predominant function in wound treatment; however, the dressings for the long-lasting and non-healing wounds are still a significant challenge in the wound care management market. Astonishingly, advanced wound dressing which is embedded with a synthetic drug compound in a natural polymer compound that acts as drug release carrier has brought about promising treatment effect toward injured wound. In the current study, results have shown that Vicenin-2 (VCN-2) compound in low concentration significantly enhanced cell proliferation and migration of HDF. It also regulated the production of pro-inflammatory cytokines such as IL-6, IL-1ß, and TNF-α from HDF in wound repair. Treatment of VCN-2 also has facilitated the expression of TGF-1ß and VEGF wound healing maker in a dose-dependent manner. A hydrocolloid film based on sodium alginate (SA) incorporated with VCN-2 synthetic compound which targets to promote wound healing particularly in diabetic condition was successfully developed and optimized for its physico-chemical properties. It was discovered that all the fabricated film formulations prepared were smooth, translucent, and good with flexibility. The thickness and weight of the formulations were also found to be uniform. The hydrophilic polymer comprised of VCN-2 were shown to possess desirable wound dressing properties and superior mechanical characteristics. The drug release profiles have revealed hydrocolloid film, which is able to control and sustain the VCN-2 released to wound area. In short, hydrocolloid films consisting of VCN-2 formulations are suitably used as a potential wound dressing to promote restoration of wound injury.


Subject(s)
Apigenin , Bandages , Dermis/metabolism , Fibroblasts/metabolism , Glucosides , Membranes, Artificial , Wound Healing/drug effects , Apigenin/chemistry , Apigenin/pharmacology , Cells, Cultured , Dermis/pathology , Fibroblasts/pathology , Glucosides/chemistry , Glucosides/pharmacology , Humans
15.
J Biomater Sci Polym Ed ; 30(8): 629-645, 2019 06.
Article in English | MEDLINE | ID: mdl-30896336

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/chemistry , Carboxymethylcellulose Sodium/chemistry , Graphite/chemistry , Hydrogels/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Bandages , Biofilms , Caenorhabditis elegans/drug effects , Carboxymethylcellulose Sodium/pharmacology , Cell Line , Cell Survival , Drug Compounding/methods , Humans , Hydrogels/pharmacology , Oxidation-Reduction , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Wound Healing/drug effects
16.
BMC Complement Altern Med ; 19(1): 20, 2019 Jan 17.
Article in English | MEDLINE | ID: mdl-30654793

ABSTRACT

BACKGROUND: Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. The risk of developing diabetic foot ulcers for diabetic patients is 15% over their lifetime and approximately 85% of limb amputations is caused by non-healing ulcers. Unhealed, gangrenous wounds destroy the structural integrity of the skin, which acts as a protective barrier that prevents the invasion of external noxious agents into the body. Vicenin-2 (VCN-2) has been reported to contain prospective anti-oxidant and anti-inflammatory properties that enhance cell proliferation and migration. Sodium Alginate (SA) is a natural polysaccharide that possesses gel forming properties and has biodegradable and biocompatible characteristics. Therefore, the objective of this study is to evaluate the effect of SA wound dressings containing VCN-2 on diabetic wounds. METHODS: Wounds were inflicted in type-1 diabetic-streptozotocin (STZ) induced male Sprague Dawley rats. Subsequently, relevant groups were topically treated with the indicated concentrations (12.5, 25 and 50 µM) of VCN-2 hydrocolloid film over the study duration (14 days). The control group was treated with vehicle dressing (blank or allantoin). Wounded tissues and blood serum were collected on 0, 7 and 14 days prior to sacrifice. Appropriate wound assessments such as histological tests, nitric oxide assays, enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were conducted to confirm wound healing efficacy in the in vivo model. One-way Analysis of Variance (ANOVA) was used for statistical analysis. RESULTS: Results showed that hydrocolloid film was recapitulated with VCN-2 enhanced diabetic wound healing in a dose-dependent manner. VCN-2 reduced pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), mediators (iNOS and COX-2), and nitric oxide (NO) via the NF-κB pathway. Data suggests that the VCN-2 film facilitated healing in hyperglycemic conditions by releasing growth factors such as (VEGF and TGF-ß) to enhance cell proliferation, migration, and wound contraction via the VEGF and TGF-ß mechanism pathways. CONCLUSIONS: This study's findings suggest that VCN-2 may possess wound healing potential since topical treatment with VCN-2 hydrocolloid films effectively enhanced wound healing in hyperglycemic conditions.


Subject(s)
Alginates , Apigenin , Bandages, Hydrocolloid , Diabetic Foot/drug therapy , Glucosides , Wound Healing/drug effects , Alginates/administration & dosage , Alginates/therapeutic use , Animals , Apigenin/administration & dosage , Apigenin/pharmacology , Apigenin/therapeutic use , Disease Models, Animal , Glucosides/administration & dosage , Glucosides/pharmacology , Glucosides/therapeutic use , Male , Rats , Rats, Sprague-Dawley
17.
Drug Deliv Transl Res ; 9(2): 453-468, 2019 04.
Article in English | MEDLINE | ID: mdl-29560587

ABSTRACT

Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.


Subject(s)
Bandages , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Moringa oleifera , Plant Extracts/administration & dosage , Skin/drug effects , Wound Healing/drug effects , Animals , Collagen Type I/metabolism , Colloids , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Diet, High-Fat , Male , Plant Leaves , Rats, Sprague-Dawley , Skin/metabolism , Skin/pathology
18.
Drug Deliv Transl Res ; 9(2): 469-481, 2019 04.
Article in English | MEDLINE | ID: mdl-29159691

ABSTRACT

Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was < 250 nm, and HC-HT CSNPs AQ cream remained stable when stored at 25 °C. TEWL and erythema intensity for 28-day application did not indicate any signs of local irritation, redness, and toxicity, which were confirmed by normal Draize skin irritation scoring system and skin hematoxylin and eosin (H&E) staining results. Comparative results of blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone level at day 0 and day 28 were not significant, indicating non-systemic toxicity. In conclusion, HC-HT CSNP AQ cream is safe, well-tolerated, and non-toxic, which may be useful in treating atopic dermatitis.


Subject(s)
Anti-Infective Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Glucocorticoids/administration & dosage , Hydrocortisone/administration & dosage , Nanoparticles/administration & dosage , Phenylethyl Alcohol/analogs & derivatives , Skin Cream/administration & dosage , Administration, Cutaneous , Adolescent , Adult , Dermatitis, Atopic/drug therapy , Double-Blind Method , Female , Humans , Middle Aged , Phenylethyl Alcohol/administration & dosage , Skin/anatomy & histology , Skin/drug effects , Young Adult
19.
Drug Deliv Transl Res ; 9(2): 508-519, 2019 04.
Article in English | MEDLINE | ID: mdl-29181832

ABSTRACT

Composite film dressings composed of pluronic F127 (PL)-pectin (PC) and pluronic (PL) F127-gelatin (GL) were investigated as potential drug delivery system for wound healing. Composite films were solvent cast by blending PL with PC or GL in different ratios using glycerol (2.5%) as plasticizer. Erythromycin (ER) (0.1%) was incorporated in films as model hydrophobic antibiotic. The optimized composite films were characterized for physical appearance, morphology, mechanical profile, and thermal behavior. In addition, drug release, antibacterial activity, and cytocompatibility of the films were investigated to assess their potential as drug delivery system. The composite films exhibited excellent wound dressing characters in terms of appearance, stability, and mechanical profile. Moreover, ER-loaded composite films released ER in controlled manner, exhibited antibacterial activity against Staphylococcus aureus, and were non-toxic to human skin fibroblast. These findings demonstrate that these composite films hold the potential to be formulated as antibacterial wound dressing.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bandages , Drug Delivery Systems , Erythromycin/administration & dosage , Poloxamer/administration & dosage , Anti-Bacterial Agents/chemistry , Cell Survival/drug effects , Cells, Cultured , Drug Liberation , Erythromycin/chemistry , Fibroblasts/drug effects , Gelatin/administration & dosage , Gelatin/chemistry , Humans , Pectins/administration & dosage , Pectins/chemistry , Poloxamer/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Wound Healing/drug effects
20.
RSC Adv ; 9(25): 14198-14208, 2019 May 07.
Article in English | MEDLINE | ID: mdl-35519311

ABSTRACT

Biofilms are gelatinous masses of microorganisms attached to wound surfaces. Previous studies suggest that biofilms generate resistance towards antibiotic treatments. It was reported that hydrogels containing xylitol and antibiotic combinations produced additive antibiofilm inhibition. However, hydrogel formulations lack specificity, due to which xylitol cannot penetrate into the biofilm matrix and gets easily degraded by bacterial beta lactamase enzymes. It was hypothesized that the incorporation of xylitol in PLGA (polylactic-co-glycolic acid) nanoparticles will enhance penetration into the EPS (extra polymeric substance) component of the biofilm matrix and potentially overcome the antibiotic resistance associated with the biofilms. The purpose of this study was to develop PLGA nanoparticles loaded with xylitol, which will enhance bacterial biofilm penetration. The nanoparticles were loaded with different amounts of xylitol (0.5-5% w/w) and characterized for physiochemical and drug release properties. The metabolic antibiofilm activity of the PLGA nanoparticles containing xylitol was demonstrated by an XTT assay using as references the cultures of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) and the polymicrobial biofilms of both bacterial strains. Live/dead viability staining was also performed to investigate the viability ratio of bacterial cells present in the biofilms. The biofilm penetration study of the PLGA nanoparticles was assessed by combining the nanoparticles with conjugated concanavalin A (Con A)-fluorescein isothiocyanate (FITC) and by viewing using confocal laser scanning electron microscopy (CLSM). In conclusion, the PLGA nanoparticles loaded with xylitol were successfully developed and were found to promote the antibiofilm activity of xylitol in infected wounds.

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