title: Design, optimization and evaluation of poly-ε-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.
authors.affiliation: Department of Pharmacy, BITS-Pilani Hyderabad Campus , Jawaharnagar, Ranga Reddy (Dist.), Andhra Pradesh , India.
authors.forename: Punna Rao
authors.initials: PR
authors.lastname: Ravi
authors.forename: Rahul
authors.initials: R
authors.lastname: Vats
authors.forename: Vikas
authors.initials: V
authors.lastname: Dalal
authors.forename: Nitin
authors.initials: N
authors.lastname: Gadekar
authors.forename: Aditya
authors.initials: A
authors.lastname: N
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002208:Caproates / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D061466:Lopinavir / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D009924:Organ Culture Techniques; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002208:Caproates; D007783:Lactones; D011108:Polymers; D061466:Lopinavir; C121056:caprolactone
keywords: Box–Behnken design; Wistar rats; design of experiments; endocytosis; everted gut sac; lopinavir; nanoparticles; pharmacokinetics; poly-ε-caprolactone