Surface-stabilized lopinavir nanoparticles enhance oral bioavailability without coadministration of ritonavir

Author: Jain Sanyog   Sharma Jagadish M   Jain Amit K   Mahajan Rahul R  

Publisher: Future Medicine

ISSN: 1743-5889

Source: Nanomedicine, Vol.8, Iss.10, 2013-10, pp. : 1639-1655

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Abstract

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).Original submitted 26 March 2012; Revised submitted 14 September 2012; Published online 25 January 2013

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