title: Enhanced bioavailability and intestinal uptake of Gemcitabine HCl loaded PLGA nanoparticles after oral delivery.
abstract: The aim of study was to formulate PLGA nanoparticles (NPs) of Gemcitabine HCl for enhanced oral bioavailability via absorption through M cells of Peyer's patches. Commercially, the drug is available as i.v. infusion due to its short half life (8-17 min), rapid metabolism and limited tumor uptake. The NPs were prepared by multiple solvent emulsification method. Optimized formulation had particle size of 166.4±2.42 nm, and entrapment of 56.48±3.63%. TEM image revealed discrete spherical structures of NPs. DSC and FTIR studies confirmed absence of interaction between drug and polymer. In vitro and ex vivo studies demonstrated sustained release from the NPs. The enhanced absorption and uptake of NPs in Caco-2 cells and in vivo absorption in intestinal tissue after oral delivery in rats was confirmed by confocal microscopy. Transport studies in Caco-2 cells confirmed 6.37-fold permeability for NPs. In vitro antiproliferative studies confirmed marked cytotoxicity of NPs on K562 leukemia cell lines. In vivo pharmacokinetic studies in rats showed 21.47-folds bioavailability enhancement from NPs. Hence, orally delivered Gemcitabine HCl loaded NPs have the potential for improving its bioavailability and avoiding side effects associated with iv infusions as well as enhancing patient compliance through "Chemotherapy at Home".
authors.affiliation: TIFAC Centre of Relevance and Excellence in NDDS, Centre for PG Studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, Gujarat, India. Electronic address: garima_ojha28@yahoo.com.
authors.forename: Garima
authors.initials: G
authors.lastname: Joshi
authors.affiliation: TIFAC Centre of Relevance and Excellence in NDDS, Centre for PG Studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, Gujarat, India. Electronic address: abhinesh.pharma@gmail.com.
authors.forename: Abhinesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: TIFAC Centre of Relevance and Excellence in NDDS, Centre for PG Studies and Research, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, Gujarat, India. Electronic address: dr_krutikasawant@rediffmail.com.
authors.forename: Krutika
authors.initials: K
authors.lastname: Sawant
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D020014:K562 Cells; D019344:Lactic Acid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017208:Rats, Wistar; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000093542:Gemcitabine
keywords: Factorial design; Gemcitabine HCl; Intestinal uptake; Nanoparticles; Oral delivery; Pharmacokinetics