The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer

P. Venkatesan, Nagaprasad Puvvada, Rupesh Dash, Prashanth Kumar Bhusetty Nagesh, Devanand Sarkar, Belal Azab, Amita Pathak, Subhas C. Kundu, Paul B. Fisher, Mahitosh Mandal

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3794-3806
Number of pages13
JournalBiomaterials
Volume32
Issue number15
DOIs
StatePublished - May 1 2011

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Celecoxib
Nanocomposites
Chitosan
Durapatite
Hydroxyapatite
Colonic Neoplasms
Nanoparticles
Cell death
Tumors
Therapeutics
Cell proliferation
Zeta potential
Apoptosis
Functional groups
Neoplasms
Adenomatous Polyposis Coli
Hydrodynamics
Particle size
Cells
Cytoskeleton

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer. / Venkatesan, P.; Puvvada, Nagaprasad; Dash, Rupesh; Bhusetty Nagesh, Prashanth Kumar; Sarkar, Devanand; Azab, Belal; Pathak, Amita; Kundu, Subhas C.; Fisher, Paul B.; Mandal, Mahitosh.

In: Biomaterials, Vol. 32, No. 15, 01.05.2011, p. 3794-3806.

Research output: Contribution to journalArticle

Venkatesan, P, Puvvada, N, Dash, R, Bhusetty Nagesh, PK, Sarkar, D, Azab, B, Pathak, A, Kundu, SC, Fisher, PB & Mandal, M 2011, 'The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer', Biomaterials, vol. 32, no. 15, pp. 3794-3806. https://doi.org/10.1016/j.biomaterials.2011.01.027
Venkatesan, P. ; Puvvada, Nagaprasad ; Dash, Rupesh ; Bhusetty Nagesh, Prashanth Kumar ; Sarkar, Devanand ; Azab, Belal ; Pathak, Amita ; Kundu, Subhas C. ; Fisher, Paul B. ; Mandal, Mahitosh. / The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer. In: Biomaterials. 2011 ; Vol. 32, No. 15. pp. 3794-3806.
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