Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing.

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 - time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Patents review in siRNA delivery for pulmonary disorders.

siRNA inhibits protein expression by degrading complementary mRNA sequence and hence, it is widely applicable for the treatment of various diseases where single or multiple gene knock down is necessary. Due to the severity and lethality of pulmonary diseases, siRNA has been focused for improved health in these diseases. Pulmonary accumulation of siRNA can be achieved by different means like intranasal or inhalation administration or intratracheal route which is mainly utilized for in vivo animal studies. However, various pulmonary obstacles and intracellular barriers for siRNA transport challenge this novel therapeutic moiety. Researchers have utilized different viral and non-viral delivery vectors for intracellular delivery of siRNA to knock down target mRNA. The promise of RNA interference, mediated by siRNAs, has revolutionized the prospects for modulating gene expression as a way to achieve therapeutic aims in disease treatment. This review focuses on patents describing the siRNA delivery either in naked form or along with a single/multiple delivery vectors. Many inventors have shown promising results for pulmonary utilization of siRNA and more concentration on delivery system may make this genomic approach available to the clinics soon.

Suppression of cytokine gene expression and improved therapeutic efficacy of microemulsion-based tacrolimus cream for atopic dermatitis.

Tacrolimus ointment being occlusive is known to give higher dermal penetration but offers limited patient acceptance in treatment of atopic dermatitis, especially in tropical countries. Hence, the aim of this study was to develop, characterize, and evaluate a microemulsion-based cream formulation of tacrolimus against ointment in hapten-induced murine model of dermatitis. Tacrolimus-loaded microemulsion having mean globule size below 25 nm was mixed with cetomacrogol cream base. The microemulsion-based cream exhibited a significantly faster drug release through semipermeable cellulose acetate membrane in comparison to commercially available ointment. The drug retention in rodent and human cadaver skin with cream was almost twofold greater in comparison to the commercially available ointment. Further, in vivo evaluation using a fluorescent marker revealed a greater and deeper accumulation of marker in skin with cream. In vivo studies in mice revealed a prompt and significant reduction in ear swelling. The reduction in inflammatory cytokine gene expression as evaluated by semiquantitative reverse transcriptase polymerase chain reaction was also significantly higher with cream. The better efficacy of cream was reflected in histopathology as well as in morphological observations at the site of application. Thus, microemulsion-based cream presents a possibility of development of an efficacious cream vehicle and a scope for dose reduction which needs to be confirmed in clinical studies.