Development and Characterisation of Ursolic Acid Nanocrystals Without Stabiliser Having Improved Dissolution Rate and In Vitro Anticancer Activity
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 1
Abstract
Ursolic acid (UA), which is a natural pentacyclic triterpenoid, has the potential to be developed as an anticancer drug, whereas its poor aqueous solubility and dissolution rate limit its clinical application. The aim of the present study was to develop UA nanocrystals to enhance its aqueous dispersibility, dissolution rate and anticancer activity. Following the investigation on the effects of stabiliser, the ratio of organic phase to aqueous solution and drug concentration, the UA nanocrystals without stabiliser were successfully prepared by anti-solvent precipitation approach. The nanocrystals maintained similar crystallinity with particle size, polydispersion index and zeta potential values of 188.0 ± 4.4 nm, 0.154 ± 0.022, and −25.0 ± 5.9 mV, respectively. Compared with the raw material, the UA nanocrystals showed good aqueous dispensability and a higher dissolution rate, and they could be completely dissolved in 0.5% SDS solution within 120 min. Moreover, the suspension of UA nanocrystals was physically stable after storage at 4°C for 7 weeks. By inducing G2/M phase cell cycle arrest, the UA nanocrystals significantly induced stronger cell growth inhibition activity against MCF-7 cells compared with free drug in vitro, although the uptake of free UA was approximately twice higher than that of the UA nanocrystals. The UA nanocrystals may be used as a potential delivery formulation for intravenous injection with enhanced dissolution velocity and anticancer activity.
Authors and Affiliations
Ju Song, Yancai Wang, Yuelin Song, Hokman Chan, Chao Bi, Xiao Yang, Ru Yan, Yitao Wang, Ying Zheng
Keywords
Related Articles
- EP ID EP682325
- DOI 10.1208/s12249-013-0028-0
- Views 68
- Downloads 0
The Comparison of Fluid Dynamics Parameters in an Andersen Cascade Impactor Equipped With and Without a Preseparator
The fluid dynamic data in Andersen cascade impactor (ACI) are still lacking. Airflows and those affected parameters can be predicted in a preseparator and Andersen cascade impactor (ACI) by computational modeling. This s...
Development and Characterization of Sorbitan Monostearate and Sesame Oil-Based Organogels for Topical Delivery of Antimicrobials
The online version of this article (doi:10.1208/s12249-014-0223-7) contains supplementary material, which is available to authorized users.
SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer
SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubilit...
Application of Physiologically Based Absorption Modeling to Formulation Development of a Low Solubility, Low Permeability Weak Base: Mechanistic Investigation of Food Effect
Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the underlying mechanisms of the observed positiv...
Microscopic Modeling of País Grape Seed Extract Absorption in the Small Intestine
The concentration profiles and the absorbed fraction (F) of the País grape seed extract in the human small intestine were obtained using a microscopic model simulation that accounts for the extracts' dissolution...