Antitumor efficacy of solid dispersion of paclitaxel prepared by supercritical antisolvent process in human mammary tumor xenografts

Title
Antitumor efficacy of solid dispersion of paclitaxel prepared by supercritical antisolvent process in human mammary tumor xenografts
Author(s)
용철순최한곤[최한곤]지상철[지상철]스리니바산 샨무간[스리니바산 샨무간]박재현[박재현]우종수[우종수]
Keywords
ALBUMIN-BOUND PACLITAXEL; BREAST-CANCER; MOLECULAR DISPERSIONS; CREMOPHOR-FREE; NUDE-MICE; TAXOL; NANOPARTICLES; INDOMETHACIN; FORMULATION; DELIVERY
Issue Date
201101
Publisher
ELSEVIER SCIENCE BV
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.403, no.1-2, pp.130 - 135
Abstract
The efficacy of intravenous chemotherapy for breast cancer has been improving with newer agents. However, the fractional improvements in breast cancer progression-free survival were quite modest and these small gains are obtained at the cost of significant toxicity. To address this problem, paclitaxel solid dispersion (PSD), a Cremophor EL-free formulation prepared by supercritical antisolvent process using hydrophilic polymers as carrier, was developed to avoid Cremophor EL-associated toxicities in Taxol (R). In this study, we investigated the antitumor activity of PSD as a function of dose from 12 to 24 mg/kg (dose-effect) and compared antitumor activity of 18 mg/kg dose of PSD to that of Taxol (R) (relative efficacy) in female athymic mice bearing mammary tumor xenografts. In dose-effect study. PSD showed excellent activity and good tolerance at all doses tested with a significant increase in tumor growth inhibition, recurrence time, survival percent, and number of tumor free survivors compared to control (P<0.01). In all of the four doses tested in this study, the magnitude of the increase in effectiveness of PSD was quite substantial and statistically significant with similar degrees of weight loss. In relative efficacy study of PSD and Taxol (R), PSD demonstrated a greater degree of tumor growth inhibition with 10 complete tumor regressions (100%) and eight tumor-free survivors (80% cure). Besides, mice treated with PSD regained their initial body weight by day 27 following initial acute weight reductions, whereas mice treated with Taxol (R) required more than 40 days to regain their initial weight. In conclusion, PSD prepared by supercritical process was very effective and safe, without Cremophor EL-associated toxicities of Taxol (R), in human mammary tumor xenografts with possibilities of dose escalation. (C) 2010 Elsevier B.V. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/25773http://dx.doi.org/10.1016/j.ijpharm.2010.10.033
ISSN
0378-5173
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