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.

Development of bicalutamide-loaded PLGA nanoparticles: preparation, characterization and in-vitro evaluation for the treatment of prostate cancer

“…On the other hand Bicalutamide loaded optimized formulation exhibit less intensity of the diffraction peak compared to pure drug. This clearly indicate that the encapsulation of the Bicalutamide within the PLGA polymer (Venkatesh et al 2015).…”

Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

“…All other chemicals used in this study were of analytical grade. (Venkatesh et al, 2015) The nanoprecipation technique was the method of choice for the preparation of the nanoparticles as previously described (Venkatesh et al, 2015). Briefly, LND (20 mg) and PLGA (100 mg) were dissolved in dichlromethane (5 mL; Solution A) and were subjected to sonication for 5 min to dissolve all substances.125 mg of Poloxamer F-127 was dissolved in 50 mL of deionized water (Solution B).…”

“…Drug loading has a very important influence in the polymeric NPs preference over others such as solid lipid NPs. The improper entrapment leads to the initial burst of the NPs, which hinders its sustained release property (Venkatesh et al, 2015). Hence, the batch with highest entrapment efficiency (78±0.92%) and drug loading (32±0.37%) was chosen as formulation of choice for further characterization.…”

Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers

“…Tang et al [144] have prepared NPs based on poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers and anti-CD45RO antibody conjugated with suberoylanilide hydroxamic acid (SAHA) and NFV and tested theirs in vitro properties on ACH-2 cells. More complex studies have been performed by Venkatesh et al [145] PLGA NPs loaded with NFV have significantly enhanced the oral bioavailability of the drug studied in vivo in New Zealand rabbits, a reduced frequency of dosing being needed in this case.…”