Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical: improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats

Drug Deliv. 2022 Dec;29(1):2694-2704. doi: 10.1080/10717544.2022.2110997.

Abstract

Diabetes mellitus is a life-threatening metabolic disease. At the moment, there is no effective treatment available to combat it. In this study, we aimed to develop berberine-loaded bilosomes (BER-BLS) to boost the oral bioavailability and therapeutic efficacy of berberine, a natural antidiabetic medication. The BER-BLS was fabricated using a thin-film hydration strategy and optimized using a central composite design (face-centered). The average vesicle size, entrapment efficiency, and surface charge of the optimized BER-BLS preparation were 196.5 nm, 89.7%, (-) 36.4 mV, respectively. In addition, it exhibited higher stability and better-sustained release of berberine than the berberine solution (BER-SOL). BER-BLS and BER-SOL were administered to streptozocin-induced diabetic rats. The optimized BER-BLS formulation had a significant hypoglycemic impact, with a maximum blood glucose decrease of 41%, whereas BER-SOL only reduced blood glucose by 19%. Furthermore, the pharmacological effect of oral BER-BLS and BER-SOL corresponded to 99.3% and 31.7%, respectively, when compared to subcutaneous insulin (1 IU). A pharmacokinetic analysis found a 6.4-fold rise in the relative bioavailability of berberine in BER-BLS when compared to BER-SOL at a dosage of 100 mg/kg body weight. Histopathological investigation revealed that BER-BLS is suitable for oral administration. Our data demonstrate that BLS is a potential nanocarrier for berberine administration, enhancing its oral bioavailability and antidiabetic activity.

Keywords: Berberine; bile salts; bilosomes; bioavailability; diabetes mellitus; optimization; pharmacokinetics.

MeSH terms

  • Administration, Oral
  • Animals
  • Berberine*
  • Blood Glucose
  • Diabetes Mellitus, Experimental* / drug therapy
  • Dietary Supplements
  • Hypoglycemic Agents / pharmacology
  • Particle Size
  • Rats

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Berberine

Grants and funding

This work was funded by the Deanship of Scientific Research at Jouf University under Grant Number (DSR2022-RG-0143).