RESUMO
Ulceration of the foot in diabetes is common and disabling, and frequently leads to amputation of the leg. The pathogenesis of foot ulceration is complex, clinical presentation variable and management requires early expert assessment. Despite treatment, ulcers readily become chronic wounds. Chronic wounds are those that remain in a chronic inflammatory state failing a normal healing process patterns. This is partially caused by inefficient eradication of opportunistic pathogens like Pseudomonas aeruginosa. We propose its control or eradication will promote wound healing. Lactobacillus plantarum cultures supernatants (LAPS) shows antipathogenic and pro-healing properties. The main objective was to design two pharmaceutical dosage forms by using LAPS as active pharmaceutical ingredient and to perform its quality control, in vitro activity conservation tests and human trials (safety evaluation). Both selected formulations reach the technological quality expected for 120 days, shows adequate occlusive characteristics and proper adhesion to human skin. From the in vitro release assays were found that LAPS shows adequate release from matrix and maintain its antimicrobial and anti-biofilm activity. First human trials were developed and neither edema nor erythema on healthy skin voluntaries was found. We conclude that C80 and C100 are adequate for their use in future clinical trials to demonstrate a comprehensive therapeutic effectiveness in ischemic chronic wounds.
Assuntos
Antibacterianos/farmacologia , Técnicas de Cultura de Células , Meios de Cultivo Condicionados/farmacologia , Lactobacillus plantarum/crescimento & desenvolvimento , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Meios de Cultivo Condicionados/efeitos adversos , Meios de Cultivo Condicionados/química , Humanos , Lactobacillus plantarum/química , Pseudomonas aeruginosa/fisiologiaRESUMO
CONTEXT: In countries where research budgets are meager as Argentina, the tendency to innovation and improvements in the designs prototypes "made in Argentina" marks a growing trend adopted by researchers. This article presents a diffusion cell of original design, for release studies of Active Pharmaceutical Ingredient (API) from classical topical dosage forms, also includes the methodology for its optimization and validation. The objective was to evaluate and validate a system designed and to compare it to the Franz cells system. METHODS: Parameters, reproducibility and robustness were performed included factors as, stirring conditions, membrane stabilization treatment and temperature variation. Release and retention on membrane assay were performed using two different API and formulations. RESULTS: The method is reproducible and robust for the parameters tested. Release assays show that no significative difference with the Franz Cells system. Our system allows the simultaneous measurement of different parameters, representing an innovation on these methodologies. The LMC was used for assays of in vitro retention on membrane and the values obtained were reproducible and coincident whit values obtained for other authors. CONCLUSIONS: The system designed and the methodology employed, are acceptable for in vitro release studies. The device and method has the characteristics required.
Assuntos
Química Farmacêutica/instrumentação , Liberação Controlada de Fármacos , Membranas Artificiais , Preparações Farmacêuticas/administração & dosagem , Administração Tópica , Química Farmacêutica/métodos , Difusão , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Desenho de Equipamento , Pomadas/química , Permetrina/administração & dosagem , Permetrina/química , Preparações Farmacêuticas/química , Reprodutibilidade dos TestesRESUMO
Chronic wounds are those that remain in a chronic inflammatory state and fail to follow normal healing process. Infection is one of the most important causes of chronicity. A frequent pathogen isolated from chronic infections is Pseudomonas aeruginosa; refractory to therapy and host immune attack in its biofilm phenotype. Lactobacillus plantarum cultures supernatants (LAPS) interfere with its pathogenic capacity. In addition, LAPS showed bacteriostatic and bactericide properties and is neither cytotoxic nor an inductor of necrosis-apoptosis. LAPSs chemical composition was determined; allowing us to propose a correlation between its constituents and their biological activity. This article shows a pharmaceutical dosage form designed by using LAPS as an API with pro-healing activity and its quality control. Pharmacotechnical and anti-microbial assays were adapted to demonstrate that the vehicle used does not modify LAPS activities. Selected formulation (F100) showed fair mechanical and technological properties. From the in vitro release assays was found an adequate release from the carrier matrix and maintains its anti-pathogenic activity for 6 months. We propose F100 for chronic wounds treatment. The use of harmless bacteria by-products, such as LAPS, to antagonize infectious pathogens that have ability to form biofilm is an efficient and economic approach to treat infected chronic wounds.