NSTI BioNano 2010

Modified glycol chitosan nanocarriers carry hydrophobic materials into tumours

A. Raza, M. de-la Fuente, I.F. Uchegbu, A. Schätzlein
Nuclear Medicines Oncology & Radiotherapy Institute, PK

Keywords: modified glycol chitosan, nanocarriers, etoposide, xenograft, polysoaps, nile red


Etoposide is a potent anticancer drug commonly used in a variety of malignancies. High protein binding, requirement of fairly high doses of drugs to achieve sustained plasma levels and hypersensitivty issues are related to its use. One promising alternative for the efficient delivery of etoposide to tumoral tissue relies on the use of nanocarriers that could efficiently encapsulate and release hydrophobic drugs to the target site, while decreasing undesired collateral effects. The group has previously developed a variety of modified amphiphilic glycol chitosan (GPC) based polysoaps which can form nano size clusters that has the capability of efficiently encapsulating hydrophobic drugs molecules increasing bioavailability e.g. in the gut or across the blood-brain-barrier. In current study a etoposide-GPC formulation is prepared and well characterized using NMR, gel permeation chromatography, multi angle light scattering and photon correlation spectroscopy. Stability of the formulation was checked for 3 months. Uptake of the micellar payload into cancer cells was studied in breast and ovarian cancer cells. Hydrophobic probe nile-red was selected as a model compound, and the cell uptake was evaluated by confocal microscopy. Results showed an enhanced uptake from nile red-GCP nanoparticles compared to compound in solution. The ability of these carriers to deliver their payload to solid tumors was studied in A431 xenograft models intravenously. Nile red-GCP micelles lead to higher levels of fluorescence in tumor. The study suggests that GCP micelles could serve to improve transport of hydrophobic compounds into tumors, thus potentially leading to improved therapies.
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