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


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).


CONCLUSIONS
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).
Center for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Sector 67, SAS Nagar (Mohali), Punjab 160062, India.
Sanyog
S
Jain
Jagadish M
JM
Sharma
Amit K
AK
Jain
Rahul R
RR
Mahajan
D000284:Administration, Oral; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D001682:Biological Availability; D061466:Lopinavir / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D019438:Ritonavir / Q000008:administration & dosage; D013499:Surface Properties
D044966:Anti-Retroviral Agents; D061466:Lopinavir; D019438:Ritonavir