TY - JOUR
T1 - The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer
AU - Venkatesan, P.
AU - Puvvada, Nagaprasad
AU - Dash, Rupesh
AU - Prashanth Kumar, B. N.
AU - Sarkar, Devanand
AU - Azab, Belal
AU - Pathak, Amita
AU - Kundu, Subhas C.
AU - Fisher, Paul B.
AU - Mandal, Mahitosh
N1 - Funding Information:
We are grateful to Aarthi Drug Ltd., for generously providing celecoxib. We wish to thank Mr. Debashis Gayen for skilled technical assistance in confocal laser fluorescence microscopy. This work was supported by funds from the School of Medical Science and Technology , Indian Institute of Technology, Kharagpur, India . Further, the Department of Science and Technology and Department of Biotechnology, New Delhi supported our work financially (to SCK and MM). SCK wishes to acknowledge to Indo-US science & Technology Forum, New Delhi for his visit to USA. Dr. Devanand Sarkar is a Harrison Scholar and Dr. Paul B. Fisher holds the Thelma Newmeyer Corman Chair in Cancer Research in the VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine. SCK and MM are also grateful to professor Paul Fisher, VCU Institute of Molecular Genetics for his kind hospitality during their short stay.
PY - 2011/5
Y1 - 2011/5
N2 - Celecoxib has shown potential anticancer activity against most carcinomas, especially in patients with familial adenomatous polyposis and precancerous disease of the colon. However, serious side effects of celecoxib restrict its generalized use for cancer therapy. In order to resolve these issues and develop an alternative strategy/preliminary approach, chitosan modified hydroxyapatite nanocarriers-mediated celecoxib delivery represents a viable strategy. We characterized the nanoparticle for morphology, particle size, zeta potential, crystalinity, functional group analysis, entrapment efficiency, drug release and hemocompatibility. The effects of celecoxib-loaded nanoparticles on colon cancer cell proliferation, morphology, cytoskeleton, cellular uptake and apoptosis were analysed in vitro. Further, we evaluated the antiproliferative, apoptotic and tumor inhibitory efficacy of celecoxib-loaded nanocarriers in a nude mouse human xenograft model. Nanoparticles exhibited small, narrow hydrodynamic size distributions, hemocompatibility, high entrapment efficiencies and sustained release profiles. In vitro studies showed significant antiproliferation, apoptosis and time-dependent cytoplasmic uptake of celecoxib-loaded Hap-Cht nanoparticles in HCT 15 and HT 29 colon cancer cells. Additional in vivo studies demonstrated significantly greater inhibition of tumor growth following treatment with this modified nanoparticle system. The present study indicates a promising, effective and safe means of using celecoxib, and potentially other therapeutic agents for colon cancer therapy.
AB - Celecoxib has shown potential anticancer activity against most carcinomas, especially in patients with familial adenomatous polyposis and precancerous disease of the colon. However, serious side effects of celecoxib restrict its generalized use for cancer therapy. In order to resolve these issues and develop an alternative strategy/preliminary approach, chitosan modified hydroxyapatite nanocarriers-mediated celecoxib delivery represents a viable strategy. We characterized the nanoparticle for morphology, particle size, zeta potential, crystalinity, functional group analysis, entrapment efficiency, drug release and hemocompatibility. The effects of celecoxib-loaded nanoparticles on colon cancer cell proliferation, morphology, cytoskeleton, cellular uptake and apoptosis were analysed in vitro. Further, we evaluated the antiproliferative, apoptotic and tumor inhibitory efficacy of celecoxib-loaded nanocarriers in a nude mouse human xenograft model. Nanoparticles exhibited small, narrow hydrodynamic size distributions, hemocompatibility, high entrapment efficiencies and sustained release profiles. In vitro studies showed significant antiproliferation, apoptosis and time-dependent cytoplasmic uptake of celecoxib-loaded Hap-Cht nanoparticles in HCT 15 and HT 29 colon cancer cells. Additional in vivo studies demonstrated significantly greater inhibition of tumor growth following treatment with this modified nanoparticle system. The present study indicates a promising, effective and safe means of using celecoxib, and potentially other therapeutic agents for colon cancer therapy.
KW - Celecoxib
KW - Colon cancer
KW - Inhibition
KW - Nanocomposite
KW - Xenograft
UR - http://www.scopus.com/inward/record.url?scp=79952745543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952745543&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2011.01.027
DO - 10.1016/j.biomaterials.2011.01.027
M3 - Article
C2 - 21392822
AN - SCOPUS:79952745543
SN - 0142-9612
VL - 32
SP - 3794
EP - 3806
JO - Biomaterials
JF - Biomaterials
IS - 15
ER -