Intravenous hydrophobic drug delivery: a porous particle formulation of paclitaxel (AI-850).

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Straub JA, Chickering DE, Lovely JC, Zhang H, Shah B, Waud WR, Bernstein H

Intravenous hydrophobic drug delivery: a porous particle formulation of paclitaxel (AI-850).

Pharm Res. 2005 Mar;22(3):347-55.

PubMed ID
15835739 [ View in PubMed
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Abstract

PURPOSE: To develop a rapidly dissolving porous particle formulation of paclitaxel without Cremophor EL that is appropriate for quick intravenous administration. METHODS: A rapidly dissolving porous particle formulation of paclitaxel (AI-850) was created using spray drying. AI-850 was compared to Taxol following intravenous administration in a rat pharmacokinetic study, a rat tissue distribution study, and a human xenograft mammary tumor (MDA-MB-435) model in nude mice. RESULTS: The volume of distribution and clearance for paclitaxel following intravenous bolus administration of AI-850 were 7-fold and 4-fold greater, respectively, than following intravenous bolus administration of Taxol. There were no significant differences between AI-850 and Taxol in tissue concentrations and tissue area under the curve (AUC) for the tissues examined. Nude mice implanted with mammary tumors showed improved tolerance of AI-850, enabling higher administrable does of paclitaxel, which resulted in improved efficacy as compared to Taxol administered at its maximum tolerated dose (MTD). CONCLUSIONS: The pharmacokinetic data indicate that paclitaxel in AI-850 has more rapid partitioning from the bloodstream into the tissue compartments than paclitaxel in Taxol. AI-850, administered as an intravenous injection, has been shown to have improved tolerance in rats and mice and improved efficacy in a tumor model in mice when compared to Taxol.

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