title: Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading.
abstract: SR13668 [2,10-Dicarbethoxy-6-methoxy-5,7-dihydro-indolo-(2,3-b)carbazole] has been proven effective in cancer prevention, but the limited bioavailability has hindered its clinical translation. In this study, we have developed a continuous, scalable process to form stable poly(lactic-co-glycolic acid) nanoparticles encapsulating SR13668, based on understanding of the competitive kinetics of nanoprecipitation and spray drying. The optimized formulation achieved high drug loading (33.3 wt %) and small particles (150 nm) with narrow size distribution. The prepared nanoparticle suspensions through flash nanoprecipitation were spray dried to achieve long-term stability and to conveniently adjust the nanoparticle concentration before use. In vitro release of SR13668 from the nanosuspensions was measured in a solution with separated organic and aqueous phases to overcome the limit of SR13668 low water solubility. Higher oral bioavailability of SR13668 by employing polymeric nanoparticles compared with the Labrasol® formulation was demonstrated in a mouse model.
authors: Department of Chemical Engineering, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors: Hao
authors: H
authors: Shen
authors: Aryamitra A
authors: AA
authors: Banerjee
authors: Paulina
authors: P
authors: Mlynarska
authors: Mathew
authors: M
authors: Hautman
authors: Seungpyo
authors: S
authors: Hong
authors: Izet M
authors: IM
authors: Kapetanovic
authors: Alexander V
authors: AV
authors: Lyubimov
authors: Ying
authors: Y
authors: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002227:Carbazoles; D011108:Polymers; C523402:SR 13668; D013535:Suspensions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid