In this investigation, we report the use of the
pullulan acetate, a hydrophobic derivative of
pullulan in the formulation of
Lopinavir loaded nanoparticles meant for oral delivery.
Pullulan was modified to
pullulan acetate by acetylation process in the presence of
pyridine; acetylation was confirmed by FT-IR and NMR spectra.
Lopinavir, an
HIV-protease inhibitor was formulated into nanoparticles of
pullulan acetate by the well-known
emulsion-
solvent-evaporation method. The nanoparticles were tested for particle size, entrapment efficiency, in-vitro drug release and stability. Further, extensive pharmacokinetic and tissue distribution studies were performed in Wistar rats. The results showed that, with our method, we could obtain nanoparticles of ∼197 nm, high entrapment efficiency (∼75%) and monodisperse nature (PDI<0.2). Stability data showed that the nanoparticles were stable over a period of 3 months. From the pharmacokinetic study data, we found that the relative bioavailability of
Lopinavir from nanoparticles was ∼2 folds higher than the free
drug. Moreover, the tissue distribution study showed a higher distribution of
Lopinavir loaded nanoparticles to lymphoid organs (liver, spleen and lymph nodes that are also important viral reservoirs in
HIV infection). Thus, we conclude that
Lopinavir loaded nanoparticle could be a superior alternative approach to free
Lopinavir in treating
HIV infection.