Design, optimization and evaluation of poly-ɛ-caprolactone (PCL) based polymeric nanoparticles for oral delivery of lopinavir

Abstract

Lopinavir (LPV)-loaded poly-ε-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box-Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3 nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV.

The influence of freeze drying and ϒ-irradiation in pre-clinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using D-(+)-trehalose and polyethylene glycol

“…This can be attributed to the presence of lactone residues on the polymeric matrix surface. 32 Thus, all samples being assayed were considered to be satisfactory NP suspensions.…”

Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model

“…The concomitant increase in particle size with increasing polymer, lipid, or Eto concentrations could be attributed to the increase in viscosity which inversely affects the evaporation rate of the organic solvent and opposes the effect of stirring speed to breakdown the particles into smaller ones. [ 41–43 ] On the contrary, increasing the stirring speed increases the mechanical and hydraulic shear which decreases the particle size. [ 44 ] PLGA, lecithin:tristearin, and Eto concentration, as well as, stirring speed showed a positive effect on EE %.…”

Comparative pharmacokinetic evaluation of lopinavir and lopinavir-loaded solid lipid nanoparticles in hepatic impaired rat model

“…This is because, in the drug‐loaded nanocarrier system, the drug is not available in free form. The plasma drug exposure of drug‐loaded nanocarrier system administered through any extravascular route is dependent on the absorption and disposition properties of the carrier system and how the loaded drug releases from the carrier system in the blood …”

“…The plasma drug exposure of drug-loaded nanocarrier system administered through any extravascular route is dependent on the absorption and disposition properties of the carrier system and how the loaded drug releases from the carrier system in the blood. [13,[17][18][19] It is anticipated that in patients with HIV/TB co-infection, where there are chances of drug-induced hepatotoxicity, dose adjustment (reduction) of LPV (conventional formulations) can lead to a further decrease in distribution of drug to viral reservoirs. On contrary to this, in hepatotoxic condition, nanocarrier delivery systems like SLNs would be more efficient in preventing undue plasma exposure compared with conventional formulations of LPV.…”