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Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for paclitaxel.
Eur J Pharm Biopharm 2009; 73(2):230-8EJ

Abstract

Paclitaxel (PTX) is an effective anti-cancer drug currently used to treat a wide variety of cancers. Unfortunately, nonaqueous vehicle containing Cremophor EL is associated with serious clinical side effects. This work aimed to evaluate the ability of polymeric micelles to (i) solubilize PTX without Cremophor EL and to be used as a (ii) safe and (iii) effective delivery system for PTX. Hence, we developed novel self-assembling poly(ethyleneglycol)(750)-block-poly(epsilon-caprolactone-co-trimethylenecarbonate) (PEG-p-(CL-co-TMC)) polymeric micelles which form micelles spontaneously in aqueous solution. The solubility of PTX increased up to three orders of magnitude. The PTX-loaded micelles showed a slow release of PTX with no burst effect. The HeLa cells viability assessed by the MTT test was lower for PTX-loaded micelles than for Taxol (IC(50) 10.6 vs. 17.6 microg/ml). When solubilized in micelles, PTX induced apoptosis comparable with Taxol. The maximum tolerated doses (MTD) of PTX-loaded micelles and Taxol in mice were 80 mg/kg and 13.5mg/kg, respectively, after intraperitoneal administration; and 45 mg/kg and 13.5mg/kg, respectively, after intravenous administration. Similar anti-tumor efficacy of PTX-loaded micelles and Taxol was observed at the dose of 13.5mg/kg on TLT-tumor-bearing mice, while the body weight loss was only observed in Taxol group. However, as higher dose was tolerated (80 mg/kg - IP), a higher growth delay was induced with PTX-loaded micelles. These results demonstrated that PTX-loaded self-assembling micelles present a similar anti-tumor efficacy as Taxol, but significantly reduced the toxicity allowing the increase in the dose for better therapeutic response.

Authors+Show Affiliations

Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels B-1200, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19577643

Citation

Danhier, Fabienne, et al. "Novel Self-assembling PEG-p-(CL-co-TMC) Polymeric Micelles as Safe and Effective Delivery System for Paclitaxel." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 73, no. 2, 2009, pp. 230-8.
Danhier F, Magotteaux N, Ucakar B, et al. Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for paclitaxel. Eur J Pharm Biopharm. 2009;73(2):230-8.
Danhier, F., Magotteaux, N., Ucakar, B., Lecouturier, N., Brewster, M., & Préat, V. (2009). Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for paclitaxel. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 73(2), pp. 230-8. doi:10.1016/j.ejpb.2009.06.015.
Danhier F, et al. Novel Self-assembling PEG-p-(CL-co-TMC) Polymeric Micelles as Safe and Effective Delivery System for Paclitaxel. Eur J Pharm Biopharm. 2009;73(2):230-8. PubMed PMID: 19577643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective delivery system for paclitaxel. AU - Danhier,Fabienne, AU - Magotteaux,Nicolas, AU - Ucakar,Bernard, AU - Lecouturier,Nathalie, AU - Brewster,Marcus, AU - Préat,Véronique, Y1 - 2009/07/03/ PY - 2009/04/20/received PY - 2009/06/17/revised PY - 2009/06/29/accepted PY - 2009/7/7/entrez PY - 2009/7/7/pubmed PY - 2009/12/16/medline SP - 230 EP - 8 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 73 IS - 2 N2 - Paclitaxel (PTX) is an effective anti-cancer drug currently used to treat a wide variety of cancers. Unfortunately, nonaqueous vehicle containing Cremophor EL is associated with serious clinical side effects. This work aimed to evaluate the ability of polymeric micelles to (i) solubilize PTX without Cremophor EL and to be used as a (ii) safe and (iii) effective delivery system for PTX. Hence, we developed novel self-assembling poly(ethyleneglycol)(750)-block-poly(epsilon-caprolactone-co-trimethylenecarbonate) (PEG-p-(CL-co-TMC)) polymeric micelles which form micelles spontaneously in aqueous solution. The solubility of PTX increased up to three orders of magnitude. The PTX-loaded micelles showed a slow release of PTX with no burst effect. The HeLa cells viability assessed by the MTT test was lower for PTX-loaded micelles than for Taxol (IC(50) 10.6 vs. 17.6 microg/ml). When solubilized in micelles, PTX induced apoptosis comparable with Taxol. The maximum tolerated doses (MTD) of PTX-loaded micelles and Taxol in mice were 80 mg/kg and 13.5mg/kg, respectively, after intraperitoneal administration; and 45 mg/kg and 13.5mg/kg, respectively, after intravenous administration. Similar anti-tumor efficacy of PTX-loaded micelles and Taxol was observed at the dose of 13.5mg/kg on TLT-tumor-bearing mice, while the body weight loss was only observed in Taxol group. However, as higher dose was tolerated (80 mg/kg - IP), a higher growth delay was induced with PTX-loaded micelles. These results demonstrated that PTX-loaded self-assembling micelles present a similar anti-tumor efficacy as Taxol, but significantly reduced the toxicity allowing the increase in the dose for better therapeutic response. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/19577643/Novel_self_assembling_PEG_p__CL_co_TMC__polymeric_micelles_as_safe_and_effective_delivery_system_for_paclitaxel_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(09)00207-0 DB - PRIME DP - Unbound Medicine ER -