title: The Next Generation Non-competitive Active Polyester Nanosystems for Transferrin Receptor-mediated Peroral Transport Utilizing Gambogic Acid as a Ligand.
abstract: The current methods for targeted drug delivery utilize ligands that must out-compete endogenous ligands in order to bind to the active site facilitating the transport. To address this limitation, we present a non-competitive active transport strategy to overcome intestinal barriers in the form of tunable nanosystems (NS) for transferrin receptor (TfR) utilizing gambogic acid (GA), a xanthanoid, as its ligand. The NS made using GA conjugated poly(lactide-co-glycolide) (PLGA) have shown non-competitive affinity to TfR evaluated in cell/cell-free systems. The fluorescent PLGA-GA NS exhibited significant intestinal transport and altered distribution profile compared to PLGA NS in vivo. The PLGA-GA NS loaded with cyclosporine A (CsA), a model peptide, upon peroral dosing to rodents led to maximum plasma concentration of CsA at 6 h as opposed to 24 h with PLGA-NS with at least 2-fold higher levels in brain at 72 h. The proposed approach offers new prospects for peroral drug delivery and beyond.
authors.affiliation: Department of Pharmaceutical Sciences, Texas A&M Health Science Center, Reynolds Medical Building, Mail Stop 1114, College Station 77843, Texas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Saini
authors.affiliation: Department of Pharmaceutical Sciences, Texas A&M Health Science Center, Reynolds Medical Building, Mail Stop 1114, College Station 77843, Texas, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ganugula
authors.affiliation: Department of Pharmaceutical Sciences, Texas A&M Health Science Center, Reynolds Medical Building, Mail Stop 1114, College Station 77843, Texas, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Pharmaceutical Sciences, Texas A&M Health Science Center, Reynolds Medical Building, Mail Stop 1114, College Station 77843, Texas, USA.
authors.forename: M N V Ravi
authors.initials: MN
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002474:Cell-Free System; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007422:Intestines / Q000737:chemistry*; D019344:Lactic Acid / Q000493:pharmacokinetics*; D008024:Ligands; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D008024:Ligands; D011990:Receptors, Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine