TOXICOLOGICAL EVALUATION OF NATURAL AND SYNTHETIC POLYMER BASED DISSOLVABLE MICRONEEDLE PATCHES HAVING VARIABLE RELEASE PROFILES

Abstract

Acute toxicity studies of dissolvable microneedle (dMN) patches fabricated from a combination of polymers, i.e. thiolated chitosan (TCS), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP), were performed to determine the safety of polymers on white albino rabbits. The selected albino rabbits were categorized into four groups. Group I was a control group, whereas groups II, III and IV were administered different doses of polymeric dMN patches. The food and water uptake and the weight of the animals were observed before and after administration of the microneedle patch on days 1, 3, 5, 7 and 14. Hematological and serum biochemical changes were observed by taking blood samples of treated and control group rabbits on the 15th day of study. The weight of the main organs was determined and a histopathology study was also performed. Negligible alteration in body weight, meals and water uptake was observed. The control and treated animals displayed similar behavioral pattern. Moreover, the treated groups showed hematological and biochemical analysis results, which were comparable with the results of the control group animals. Animals from both control and treated groups did not present any significant difference in the results of relative organ body weight and urine analysis. A comparison of histopathology results for both treated and control animals’ vital organs confirmed the absence of lesions. The findings of antioxidant effect, dermal and cardiac toxicity studies of chitosan, thiolated chitosan and the TCS/PVA/PVP combination were compared to those of the analysis of circulating oxidative levels, demonstrating that the combination of TCS/PVA/PVP showed improved antioxidant effect, as compared to those of chitosan and thiolated chitosan alone, and showed no significant effect on skin and heart. Thus, the findings of the study established the fact that the fabricated polymeric dMNs are a safe carrier system for different drugs.