RRC ID 68572
Author Nakamura T, Fukiage M, Higuchi M, Nakaya A, Yano I, Miyazaki J, Nishiyama H, Akaza H, Ito T, Hosokawa H, Nakayama T, Harashima H.
Title Nanoparticulation of BCG-CWS for application to bladder cancer therapy.
Journal J Control Release
Abstract 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.
Volume 176
Pages 44-53
Published 2014-2-28
DOI 10.1016/j.jconrel.2013.12.027
PII S0168-3659(13)00969-3
PMID 24389133
MeSH Adult Animals Antineoplastic Agents / administration & dosage* Butylhydroxybutylnitrosamine Cell Differentiation / drug effects Cell Line, Tumor Cell Wall Skeleton / administration & dosage* Cells, Cultured Female Humans Male Mice Mice, Inbred C3H Mycobacterium bovis* Nanoparticles / administration & dosage* Rats Rats, Inbred F344 T-Lymphocytes / cytology T-Lymphocytes / drug effects Urinary Bladder Neoplasms / chemically induced Urinary Bladder Neoplasms / drug therapy* Young Adult
IF 7.727
Human and Animal Cells MBT-2(RCB0544)