Quality by design-based optimization of formulation and process parameters for berberine nanosuspension for enhancing its dissolution rate, bioavailability, and cardioprotective activity.

Abstract

Berberine (BER) possesses dissolution rate limited oral bioavailability. The present study deciphers the formulation of nanosuspension loaded with BER for enhancing its cardioprotective potential. The nanosuspension was prepared by a liquid antisolvent precipitation technique using sodium lauryl sulfate as a surfactant and polyvinyl pyrrolidone K30 (PVP K30) as a polymer. The optimized formulation showed a particle size of 251.32 ± 4.18 nm, zeta potential of -24.10 ± 1.16 mV, and drug loading capacity of 98.22 ± 2.24%. The results showed about 6.01-fold and 3.54-fold enhancement in the dissolution rate and permeability, respectively, upon loading berberine into nanosuspension. About 8.44-fold increase in Cmax , 27.22-fold increase in AUC0-t , and 27.38-fold increase in AUC0-∞ were observed in the case of BER nanosuspension, compared to its naïve form. The results of particle size, zeta potential, and drug loading showed a nonsignificant change in the response of fresh and aged nanosuspension, which indicated that the formulation was stable. In vitro results on H9C2 cell line indicated a lower cellular proliferation rate after treatment with BER nanosuspension with decreased cytoplasmic expression of angiotensin converting enzyme (ACE) protein. Overall, the results indicated the successful development of BER nanosuspension with an enhanced dissolution rate, permeability, bioavailability, and cardioprotective activity. Practical applications The present study provides the evidence that the formulation of nanosuspension loaded with berberine enhance the cardioprotective activity of berberine. The results of the study supports the improved bioavailability of nanosuspension of berberine showed enhanced cardioprotective activity.