Surface-Stabilized Lopinavir Nanoparticles Enhance Oral Bioavailability Without Coadministration of Ritonavir

AIM: The aim of the present study was to prepare surface-stabilized nanoparticles (NPs) for oral bioavailability enhancement of lopinavir (LPN), a Biopharmaceutics Classification System class II antiretroviral drug that possesses low oral bioavailability due to its poor aqueous solubility and extensive metabolism by liver microsomal enzymes. MATERIALS & METHODS: Surfactant-stabilized LPN-NPs were prepared by combination of antisolvent precipitation and high-pressure homogenization techniques using polyvinyl alcohol as a suitable stabilizer. LPN-NPs were freeze dried by a universal stepwise freeze-drying cycle using mannitol as the cryoprotectant. Pharmacokinetics after oral administration of LPN-NPs were evaluated in male Sprague-Dawley rats and were compared with free LPN coadministered with ritonavir (conventional formulation). RESULTS & CONCLUSION: Freeze-dried stabilized LPN-NPs possessed particle sizes of approximately 320 nm and a narrow particle size distribution (polydispersity index <0.2). The surface-stabilized LPN-NPs (without ritonavir) demonstrated a 3.11-fold enhancement in bioavailability in comparison to free LPN with ritonavir (conventional formulation).