Formulation of Chitosan Stabilized Silver Nanoparticle-Containing Wound Healing Film: In Vitro and In Vivo Characterization.

A wound indicates a discontinuity in the epithelial integrity of the skin along with structural and functional disruption of the underlying normal tissue. The study focused on chitosan stabilized silver nanoparticles (CH-AgNP) further incorporated in a chitosan-based (CH-AgNP-CHF) film for wound healing. Dual advantages of chitosan as a wound-healing agent in addition to the antimicrobial property of CH-AgNP nanoparticles was explored. Based on preliminary trials, 1-2% w/v chitosan as film former, 15-25% w/v glycerin as plasticizer and Teflon as casting surface was selected. The optimized CH-AgNP-CHF had tensile strength 1.39 ± 0.009 N/mm2, % Elongation 33.33 ± 1.634, 76.66 ± 0.584% degree of swelling, WVTR of 2024.43 ± 32.78 gm.m-2 day-1 and 1144.57 ± 13.45 gm.m-2 day-1 after 24 h and after 21 days respectively. The CH-AgNP-CHF reported highest % inhibition of 62.22 ± 0.91 against Escherichia coli as compared to chitosan solution, chitosan film and CH-AgNP solution. Based on in vivo animal study, CH-AgNP-CHF showed highest wound closure rate at 3rd, 5th, 7th, 14th and 21st day to indicate better and faster wound healing compared to marketed SilverKind® Nanofine gel, blank chitosan film and sterile gauze treated group (Control). Thus, CH-AgNP-CHF is more effective alternative for wound healing.

In vitro and in vivo evaluation of gentamicin sulphate-loaded PLGA nanoparticle-based film for the treatment of surgical site infection.

The study focuses on the in vitro and in vivo evaluation of the developed gentamicin sulphate (GS)-loaded poly lactic-co-glycolic acid (PLGA) nanoparticle (PNP)-based pullulan film (PNP-F). Sterilization being an essential pre-requisite for the dosage form was carried out using ethylene oxide. Post-sterilization, PNP-F was evaluated for mechanical properties, percentage drug loading, antimicrobial effectiveness study, test for sterility and in vitro dissolution study using Strat-M® membrane. In vitro dissolution study revealed that GS gradually released from PNP-F and the highest cumulative percentage drug release was found to be 86.76 ± 0.03% at 192 h. Wound healing assay was performed to study the effect of PNP-F over migratory potential of dermal fibroblast cells (NIH-3T3) in the presence of micro-organisms, Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). PNP-F inhibited the growth of PA and SA, allowing the growth of fibroblast cells indicating its suitability for application. In vivo study of surgical site was performed by superficial incision model in Wistar rats. Measurement of in vivo incision healing confirmed faster wound healing in the incision which received PNP-F compared to marketed cream containing GS. Graphical abstract.

Formulation development and in vitro evaluation of gentamicin sulfate-loaded PLGA nanoparticles based film for the treatment of surgical site infection by Box-Behnken design.

OBJECTIVE: Gentamicin sulfate (GS)-loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (PNPs) were developed and incorporated in film for the treatment of surgical site infection (SSI). METHOD: PNPs were prepared by double emulsification solvent removal technique using ethyl acetate solution containing PLGA and polyvinyl alcohol (PVA) as an emulsifier. The emulsion was re-emulsified using Gum Kondagogu (GKK). PNPs loaded film was prepared with 5% w/v solution of pullulan in PNPs using solvent casting technique. Design of Experiment (DoE) study using Box-Behnken design was performed for the optimization of PNPs. Drug release study was carried out for PNPs at phosphate buffer saline (PBS) pH 6.4 and simulated wound fluid (SWF) pH 7.4. RESULT: PNPs were found to have average particle size 280 ± 12.04 nm, polydispersity index (PDI) 0.15 ± 0.01 and zeta potential - 4.9 ± 0.84 mV. Scanning electron microscopy (SEM) showed spherical nature of PNPs along with particle size of 160 ± 35.30 nm confirmed with transmission electron microscopy (TEM). PNPs were found to be effective against Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). Optimized batch of film showed in vitro disintegration time below 8 min with tensile strength (TS) 0.06 ± 0.03 N/cm2 and percentage elongation (% E) 70.95 ± 4.29. X-ray diffraction study (XRD) confirmed amorphous nature of GS, PLGA, pullulan, GKK and film. CONCLUSION: PNPs showed controlled release of GS after an initial burst release. Developed film can be an effective approach for management of SSI and control of antibiotic induced drug resistance.

Formulation Optimization of Chitosan-Stabilized Silver Nanoparticles Using In Vitro Antimicrobial Assay.

Antimicrobial resistance at the infected site is a serious medical issue that increases patient morbidity and mortality. Silver has antibacterial activity associated with some dose-dependent toxicity. Silver nanoparticles, due to larger surface area, have antibacterial properties, which make them useful in the treatment of infections. Chitosan-stabilized silver nanoparticles (CH-AgNP) were formulated and evaluated for minimal inhibitory concentration and minimal bactericidal concentration testing against Staphylococcus aureus ATCC 29213, S aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, and 20 methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration study was used to evaluate the biofilm reduction, and in vitro antimicrobial checkerboard assays were performed. The effective optimum ratio of AgNP:chitosan solution was 1:4. Minimal inhibitory concentration and minimal bactericidal concentration ranges of CH-AgNP were 4 to 14 times lower compared to AgNP alone against methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration values of CH-AgNP for ATCC PA-01, P aeruginosa isolate 1, and P aeruginosa isolate 2 were found to be >84.59 µg/mL, 42.29 µg/mL, and 21.15 µg/mL, respectively. Thus, CH-AgNP is a potential formulation for wound treatment and management of infected sites associated with antimicrobial resistance.

Formulation, development and characterization of mucoadhesive film for treatment of vaginal candidiasis.

OBJECTIVE: The objective of the present investigation was formulation, optimization and characterization of mucoadhesive film of clotrimazole (CT) which is patient-convenient and provides an effective alternative for the treatment of vaginal candidiasis. CT is an antimycotic drug applied locally for the treatment of vaginal candidiasis. MATERIALS AND METHODS: Mucoadhesive vaginal films were prepared by solvent casting technique using hydroxyl propylcellulose and sodium alginate as polymers. Propylene glycol and polyethylene glycol-400 were evaluated as plasticizers. The mucoadhesive vaginal films were evaluated for percentage elongation, tensile strength, folding endurance, drug content, in vitro disintegration time, in vitro dissolution study, swelling index, bioadhesive strength, and diffusion study. RESULTS: Among various permeation enhancers used, isopropyl myristate was found to be suitable. To evaluate the role of the concentration of permeation enhancer and concentration of polymers in the optimization of mucoadhesive vaginal film, 3(2) full factorial design was employed. Optimized batch showed in vitro disintegration time, 18 min; drug content, 99.83%; and tensile strength, 502.1 g/mm(2). In vitro diffusion study showed that 77% drug diffusion occurred in 6 h. This batch was further evaluated by scanning electron microscopy indicating uniformity of the film. In vitro Lactobacillus inhibition and in vitro antifungal activity of optimized batch showed an inhibitory effect against Candida albicans and no effect on Lactobacillus, which is a normal component of vaginal flora. CONCLUSION: Mucoadhesive vaginal film of CT is an effective dosage form for the treatment of vaginal candidiasis.