A novel nanoproliposomes of lercanidipine: Development, in vitro and preclinical studies to support its effectiveness in hypertension therapy.

Aim: The aim of the present study was to develop nanoproliposomes of lercanidipine, in order to overcome its poor biopharmaceutical properties and to improve its therapeutic efficacy in treating hypertension.

Main Methods: The nanoproliposomes were prepared using a modified thin-film hydration method, and the formula was optimized by varying the ratio of lipids and the types of cryoprotectants. This optimized formulation was characterized in terms of its particle size, solid-state, drug release, in-situ absorption, in-vivo pharmacokinetics, and in-vivo anti-hypertensive activity in DOCA-salt induced hypertensive rats. Finally, a PK-PD correlation was established in order to understand the clinical implications of the developed novel nanoproliposomes.

Key Findings: The nanoproliposomes showed a particle size of 174.7nm and an entrapment efficiency of 85.4%. The in-vitro release displayed initial rapid release (19.33%) followed by a sustained release profile, releasing 88.37% of the encapsulated drug. The in-situ studies showed a significant increase in absorption rate across the rat intestinal membrane. The pharmacokinetics of this novel form indicated a 2.75-fold increase in the absolute bioavailability as compared to pure lercanidipine. In addition, the nanoproliposomes were found to be efficient in treating hypertension in DOCA-salt induced hypertensive rats. The PK-PD correlation demonstrated no time lag between effect and exposure, indicating that a direct PK-PD relationship can be expected in the clinic.

Significance: These findings suggest that nanoproliposomes are promising carriers in improving the oral bioavailability and bioactivity of lercanidipine, and can be an effective therapy in the management of hypertension.