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.
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Authors | Hao Shen, Aryamitra A Banerjee, Paulina Mlynarska, Mathew Hautman, Seungpyo Hong, Izet M Kapetanovic, Alexander V Lyubimov, Ying Liu |
Journal | Journal of pharmaceutical sciences
(J Pharm Sci)
Vol. 101
Issue 10
Pg. 3877-85
(Oct 2012)
ISSN: 1520-6017 [Electronic] United States |
PMID | 22821759
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2012 Wiley-Liss, Inc. |
Chemical References |
- Carbazoles
- Polymers
- SR 13668
- Suspensions
- Polylactic Acid-Polyglycolic Acid Copolymer
- Polyglycolic Acid
- Lactic Acid
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Topics |
- Administration, Oral
- Animals
- Biological Availability
- Carbazoles
(administration & dosage, chemistry, pharmacology)
- Chemistry, Pharmaceutical
(methods)
- Drug Stability
- Kinetics
- Lactic Acid
(administration & dosage, chemistry)
- Mice
- Nanoparticles
(administration & dosage, chemistry)
- Particle Size
- Polyglycolic Acid
(administration & dosage, chemistry)
- Polylactic Acid-Polyglycolic Acid Copolymer
- Polymers
(administration & dosage, chemistry)
- Solubility
- Suspensions
(administration & dosage, chemistry, pharmacology)
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