caa a22 4500 445313579 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0428-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0428-3 Formulation, Biological and Pharmacokinetic Studies of Sucrose Ester-Stabilized Nanosuspensions of Oleanolic Acid [Elektronische Daten] [Wenji Li, Surajit Das, Ka-yun Ng, Paul Heng] ABSTRACT: Purpose: The aim of this study was to develop sucrose ester (SE)-stabilized oleanolic acid (OA) nanosuspensions (NS) for enhanced delivery. Methods: SEOA NS were prepared via O/W emulsion and organic solvent evaporation methods. The particles' size and polydispersity index were measured by nanosizer. Their percent encapsulation efficiency, saturation solubility and in vitro dissolution rate were obtained via HPLC. The in vitro bioefficacy was analyzed by MTT measurements in A549 human non-small-cell lung cancer cell line. The cellular uptake of OA and in vivo pharmacokinetics profile were determined using LC-ESI-MS/MS. Results: Spherical SEOA NS particles (~100nm in diameter) were produced and found to be physicochemically stable over a month at 4°C. In particular, SEOA 4121 NS (SEL: SEP at 4:1 w/w; SE: OA at 2:1 w/w) produced the greatest increase in saturation solubility (1.89mg/mL vs. 3.43μg/mL), dissolution rate, cytotoxicity and bioavailability. Preliminary studies indicated that cellular uptake of SEOA NS by A549 cells was temperature-, concentration- and time-dependent. Conclusion: Preparing OA as SE-stabilized NS particles provides a novel method to enhance saturation solubility, in vitro dissolution rate, bioefficacy and in vivo bioavailability of free OA and/or other potentially useful hydrophobic drugs. Springer Science+Business Media, LLC, 2011 bioavailability nationallicence dissolution rate nationallicence hydrophobic drug nationallicence oleanolic acid nationallicence saturation solubility nationallicence sucrose ester nationallicence surfactant stabilized nanosuspensions nationallicence Li Wenji Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Das Surajit Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Ng Ka-yun Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Heng Paul Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 2020-2033 0724-8741 28:8<2020 2011 28 11095 https://doi.org/10.1007/s11095-011-0428-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0428-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Wenji Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 700 1- Das Surajit Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 700 1- Ng Ka-yun Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 700 1- Heng Paul Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 2020-2033 0724-8741 28:8<2020 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer