title: Modified pullulan nanoparticles for oral delivery of lopinavir: formulation and pharmacokinetic evaluation.
abstract: 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.
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: rpunnarao@hyderabad.bits-pilani.ac.in.
authors.forename: Punna Rao
authors.initials: PR
authors.lastname: Ravi
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: rahulvats@hyderabad.bits-pilani.ac.in.
authors.forename: Rahul
authors.initials: R
authors.lastname: Vats
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: jagadeesh20191@gmail.com.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Balija
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: sathya.bitshyd@gmail.com.
authors.forename: Sathya Prabhu Naidu
authors.initials: SP
authors.lastname: Adapa
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus, Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh, India. Electronic address: aditya@hyderabad.bits-pilani.ac.in.
authors.forename: N
authors.initials: N
authors.lastname: Aditya
mesh_terms: D000107:Acetylation; D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D005936:Glucans / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D061466:Lopinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005936:Glucans; D017320:HIV Protease Inhibitors; D061466:Lopinavir; C009109:pullulan
keywords: Lopinavir; Nanoparticles; Pharmacokinetic studies; Physical characterization; Pullulan acetate; Tissue distribution