Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 20, Pages 6442-6449Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm800767c
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Funding
- Cell Dynamics Research Center
- Korean Ministry of Science and Technology
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A new platform for oral delivery of paclitaxel (PTX) was developed through chemical conjugation of PTX to a low molecular weight chitosan (LMWC). The LMWC-PTX conjugate contained similar to 12 wt % PTX and showed greatly enhanced water solubility (> 1 mg/mL) as compared to native PTX. The conjugate showed comparable IC50 values to that of the parent PTX against human cancer cell lines. The pharmacokinetic data revealed similar to 42% of bioavailability after oral administration of 5 mg PTX/kg of the conjugate. When the conjugate (10 mg/kg based on PTX content) was administered orally to mice bearing xenograft or allograft tumors, the conjugate-treated group showed significant inhibition of tumor growth, which was comparable to that seen with PTX of the clinically available injected form, formulated in cremophor EL/ethanol (iv) but with much lower toxicity. Tracking I-125-labeled conjugate showed that LMWC-PTX was likely to be absorbed mainly from the ileum and reach the blood as the intact conjugate.
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