Development of berberine-loaded PEGylated liposomes: in-vitro and ex-vivo evaluation.

OBJECTIVE

To develop and evaluate a PEGylated berberine (BE)-loaded nanoliposome formulation (Opt-BE-PEG-Ls) using a Quality by Design (QbD) approach, aimed at providing an effective, long-term antidiabetic therapeutic strategy.

SIGNIFICANCE: According to the 2024 International Diabetes Federation (IDF) Diabetes Atlas, 589 million adults (11.1%) aged 20-79 have diabetes, projected to rise to 853 million (13%) by 2050. In 2024, diabetes caused 3.4 million deaths and over USD 1 trillion in healthcare costs. The rising burden, particularly in low- and middle-income countries, underscores the urgent need for innovative and sustainable antidiabetic therapies.

METHOD: The cold injection method was utilized to prepare BE-loaded PEGylated liposomes, with formulation optimization guided by the QbD approach. Comprehensive characterization was carried out using zeta potential analysis, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). In vitro studies were also performed to evaluate the formulation. Stability testing, conducted in accordance with ICH Q1 (R2) guidelines, confirmed the formulation's robustness.

RESULT: Opt-BE-PEG-Ls were successfully optimized using a Box-Behnken Design, resulting in a particle size of 182.26 ± 0.38 nm, polydispersity index of 0.303 ± 0.003, and an entrapment efficiency of 91.07 ± 0.69%. In vitro studies demonstrated sustained drug release, strong antioxidant activity, and notable inhibition of α-amylase (86.27 ± 0.01%), α-glucosidase (70.06 ± 0.01%), and oxygen radicals (70.19 ± 0.18%).

CONCLUSION

The Opt-BE-PEG-Ls demonstrate promising potential as a stable and effective antidiabetic nano formulation, offering controlled release and strong enzymatic inhibition properties. This formulation could serve as a valuable candidate for future clinical applications in diabetes management.