title: Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect.
abstract: Nelfinavir mesylate (NFV) is an anti-viral drug, used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). Poor oral bioavailability and shorter half-life (3.5-5 h) remain a major clinical limitation of NFV leading to unpredictable drug bioavailability and frequent dosing. In this context, the objective of the present study was to formulate NFV loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which can increase the solubility and oral bioavailability along with sustained release of the drug. NFV loaded PLGA-NPs were prepared by nanoprecipitation method using PLGA and Poloxomer 407. The prepared NPs were evaluated for particle size, zeta potential, morphology, drug content, entrapment efficiency (EE) and in vitro dissolution studies. Oral bioavailability studies were carried out in New Zealand rabbits by administering developed NFV PLGA-NPs and pure drug suspension. PLGA-NPs prepared by using 1:4 ratio of drug and PLGA, with a stirring rate of 1500 rpm for 4 h. The prepared NPs were in the size of 185 ± 0.83 nm with a zeta potential of 28.7 ± 0.09 mV. The developed NPs were found to be spherical with uniform size distribution. The drug content and EE of the optimized formulation were found to be 36 ± 0.19% and 72 ± 0.47% respectively. After oral administration of NFV PLGA-NPs, the relative bioavailability was enhanced about 4.94 fold compared to NFV suspension as a control. The results describe an effective strategy for oral delivery of NFV loaded PLGA NPs that helps in enhancing bioavailability and reduce the frequency of dosing.
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India.
authors.forename: D Nagasamy
authors.initials: DN
authors.lastname: Venkatesh
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India.
authors.forename: Mahendran
authors.initials: M
authors.lastname: Baskaran
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India.
authors.forename: Veera Venkata Satyanarayana Reddy
authors.initials: VV
authors.lastname: Karri
authors.affiliation: Department of Pharmaceutical Analysis, JSS College of Pharmacy, Ootacamund, JSS University, Mysore, India ; Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
authors.forename: Sai Sandeep
authors.initials: SS
authors.lastname: Mannemala
authors.affiliation: Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, JSS University, Mysore 643001, India.
authors.forename: Kollipara
authors.initials: K
authors.lastname: Radhakrishna
authors.affiliation: Department of Pharmaceutical Analysis, JSS College of Pharmacy, Ootacamund, JSS University, Mysore, India.
authors.forename: Sandip
authors.initials: S
authors.lastname: Goti
keywords: Bioavailability; Nanoparticles; Nelfinavir mesylate; PLGA; Sustained release