The present study is concerned with the suitability of using Myrj 59, out-performing the commonly used stabilizer i.e., poloxamer, for preparation of cubosomes on one hand and gives an insight into the need for distinctive choice of delivery system and administration route towards better diabetes pharmacotherapy on the other hand. In light, repaglinide (REP) cubosomal dispersion and in-situ gel forms were prepared and physicochemically characterized. The selected cubosomal forms were tested for in-vitro drug release and administered via intranasal (IN) and intraperitoneal (IP) routes and compared with Intravenous (IV) REP solution regarding in-vivo antidiabetic efficacy. The results confirmed the formation of cubic nanostructures (170-233 nm), entrapping high REP amounts (93.2-95.66 %). Sustained REP release from selected cubosomal forms was realized with no burst release. Upon in-vivo assessment, IN and IP REP cubosomes and cubosomal gel exhibited superior long-acting in-vivo traits over IV REP solution, respecting percentages of maximum reduction, total decrease in BG levels, and the pharmacological availability. Moreover, IP REP cubosomes and cubosomal gel revealed higher values of the aforementioned parameters than IN counterparts. In conclusion, IN and IP administration of the newly developed cubosomal forms could proffer feasible options for an optimal control of BG levels.
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