The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug.
However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.
Written by:
Nakamura T, Fukiage M, Higuchi M, Nakaya A, Yano I, Miyazaki J, Nishiyama H, Akaza H, Ito T, Hosokawa H, Nakayama T, Harashima H. Are you the author?
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Japan BCG Central Laboratory, Kiyose, Japan; Department of Urology, Faculty of Medicine, Tsukuba University, Tsukuba, Japan; Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Reference: J Control Release. 2014 Feb 28;176:44-53.
doi: 10.1016/j.jconrel.2013.12.027
PubMed Abstract
PMID: 24389133
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