Modified pullulan nanoparticles for oral delivery of lopinavir: Formulation and pharmacokinetic evaluation

• Pullulan was successfully modified to formulate lopinavir loaded nanoparticles.
• Nanoparticles had high entrapment efficiency and suitable particle size.
• Nanoparticles provided metabolic protection to lopinavir against microsomal enzymes.
• Bioavailability of nanoparticles was two-fold higher compared to free drug.
• Distribution to viral reservoirs was higher for nanoparticles compared to free drug.

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.