Conjugated chitosan as a novel platform for oral delivery of paclitaxel.
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 approximately 12 wt % PTX and showed greatly enhanced water solubility (>1 mg/mL) as compared to native PTX. The conjugate showed comparable IC 50 values to that of the parent PTX against human cancer cell lines. The pharmacokinetic data revealed approximately 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.
Lee
Eunhye
E
Cell Dynamics Research Center, Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryong-dong, Gwangju 500-712, South Korea.
Lee
Jinju
J
Lee
In-Hyun
IH
Yu
Mikyung
M
Kim
Hyungjun
H
Chae
Su Young
SY
Jon
Sangyong
S
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D017239:Paclitaxel / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D000970:Antineoplastic Agents; D048271:Chitosan; D017239:Paclitaxel