In vivo efficacy of paclitaxel-loaded injectable in situ-forming gel against subcutaneous tumor growth.

Abstract

Injectable in situ-forming gels have received considerable attention as localized drug delivery systems. Here, we examined a poly(ethylene glycol)-b-polycaprolactone (MPEG-PCL) diblock copolymer gel as an injectable drug depot for paclitaxel (Ptx). The copolymer solution remained liquid at room temperature and rapidly gelled in vivo at body temperature. In vitro experiments showed that Ptx was released from MPEG-PCL copolymer gels over the course of more than 14 days. Experiments employing intratumoral injection of saline (control), gel-only, Taxol, or Ptx-loaded gel into mice bearing B16F10 tumor xenografts showed that Ptx-loaded gel inhibited the growth of B16F10 tumors more effectively than did saline or gel alone. Further, intratumoral injection of Ptx-loaded gel was more efficacious in inhibiting the growth of B16F10 tumor over 10 days than was injection of Taxol. A histological analysis demonstrated an increase in necrotic tissue in tumors treated with Ptx-loaded gel. In conclusion, our data show that intratumoral injection of Ptx-loaded MPEG-PCL diblock copolymer yielded an in situ-forming gel that exhibited controlled Ptx release profile, and that was effective in treating localized solid tumors.

• Authors: Ju Young Lee, Kyung Sook Kim, Yun Mi Kang, E Sle Kim, Sung-Joo Hwang, Hai Bang Lee, Byoung Hyun Min, Jae Ho Kim, Moon Suk Kim
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 392 Issue 1-2 Pg. 51-6 (Jun 15 2010) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 20298770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Biocompatible Materials
• Delayed-Action Preparations
• Drug Carriers
• Gels
• Polyesters
• methoxy poly(ethylene glycol-co-epsilon-caprolactone)
• Polyethylene Glycols
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, therapeutic use)
• Biocompatible Materials (chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Delayed-Action Preparations
• Drug Carriers (chemistry)
• Drug Compounding
• Drug Delivery Systems (methods)
• Gels
• Injections, Intralesional
• Injections, Subcutaneous
• Mice
• Mice, Hairless
• Neoplasms, Experimental (drug therapy, pathology)
• Paclitaxel (administration & dosage, therapeutic use)
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Solubility
• Temperature
• Viscosity
• Xenograft Model Antitumor Assays