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Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer

2009; Elsevier BV; Volume: 6; Issue: 1 Linguagem: Inglês

10.1016/j.nano.2009.03.002

1549-9642

Anekant Jain, Sanjay Jain, Narayanan Ganesh, Jaya Barve, Aadil M. Beg,

Proteoglycans and glycosaminoglycans research

Hyaluronic acid-coupled chitosan nanoparticles bearing oxaliplatin (L-OHP) encapsulated in Eudragit S100-coated pellets were developed for effective delivery to colon tumors. The in vitro drug release was investigated using a USP dissolution rate test paddle-type apparatus in different simulated gastrointestinal tract fluids. In therapeutic experiments the pellets of free drug, and hyaluronic acid-coupled and uncoupled chitosan nanoparticles bearing L-OHP were administered orally at the dose of 10 mg L-OHP/kg body weight to tumor-bearing Balb/c mice. In vivo data showed that hyaluronic acid-coupled chitosan nanoparticles delivered 1.99 +/- 0.82 and 9.36 +/- 1.10 microg of L-OHP/g of tissue in the colon and tumor, respectively after 12 hours, reflecting its targeting potential to the colon and tumor. These drug delivery systems show relatively high local drug concentration in the colonic milieu and colonic tumors with prolonged exposure time, which provides a potential to enhance antitumor efficacy with low systemic toxicity for the treatment of colon cancer.In this study, a nanoparticle system was developed to deliver oxaliplatin to colorectal tumors. In murine models, the drug delivery system showed relatively high local drug concentration in colonic tumors with prolonged exposure time, which provides a potential for enhanced antitumor efficacy with low systematic toxicity.