Enhanced oral bioavailability of a cancer preventive agent (SR13668) by employing polymeric nanoparticles with high drug loading

Hao Shen, Aryamitra A. Banerjee, Paulina Mlynarska, Mathew Hautman, Seungpyo Hong, Izet M. Kapetanovic, Alexander V. Lyubimov, Ying Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 (33.3wt %) and small particles (150nm) 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.

Original languageEnglish
Pages (from-to)3877-3885
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number10
DOIs
Publication statusPublished - 2012 Oct

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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