Development of novel nanoemulsion of pioglitazone used in the treatment of diabetes and its gel form for the treatment of skin diseases

Pioglitazone (PGL), an antidiabetic drug within the thiazolidinedione class, is utilized in managing type-2-diabetes-mellitus. Additionally, it has been observed to exhibit therapeutic effects on various inflammatory markers. PGL falls under BCS Class II, which is defined by its low water solubility and slow dissolution rate. The dual aim of our study was to optimize an oral as well as topical PGL-loaded nanoemulsion (PGL-NE) in order to enhance their bioavailability orally as well as topically. Using the Box–Behnken Design Expert software, Pioglitazone-loaded nanoemulsions (NanoE1 to NanoE17) were optimized. The ultrasonication method was employed following excipients-screening and the preparation of PTPD. The optimized nanoformulation (NanoE13) was determined based on its particle size (137.7 ± 7.92 nm), %Transmittance (91.07 ± 1.03), and PDI (0.221 ± 0.004). NanoE13 exhibited sustained drug release, adhering to the Korsemeyer-Peppas model. When converted into a gel (PGL-NE-Gel), it enhanced permeation of the skin and topical bioavailability. The results of dermatokinetic demonstrated a significant i.e., p˂0.001 increase in C_Skinmax & AUC_0–8h in skin treated with the optimized PGL-NE-Gel compared to PGL-NE and conventional PGL gel. After 2 weeks, reductions of 40.06 %, 27.34 %, and 37.45 % were observed for diabetic control, PGL-S, and PGL-NE, respectively. PGL-NE also significantly lowered the levels of blood-glucose i.e., p < 0.05 as compared to the diabetic-control -group throughout the experiment. We successfully developed a novel PGL-NE and PGL-NE-Gel, which enhanced the solubility, skin permeation, and bioavailability of Pioglitazone for both oral and topical applications.