Tumor-Penetrating Microparticles for Intraperitoneal Therapy of Ovarian Cancer
- 9 September 2008
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in The Journal of pharmacology and experimental therapeutics
- Vol. 327 (3), 673-682
- https://doi.org/10.1124/jpet.108.140095
Abstract
Intraperitoneal chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous intraperitoneal therapy used the paclitaxel/Cremophor EL (polyethoxylated castor oil) formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for intraperitoneal treatment (referred to as tumor-penetrating microparticles or TPM). Evaluation of TPM was performed using intraperitoneal metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming, whereas the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor EL: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of intraperitoneal therapy.Keywords
This publication has 42 references indexed in Scilit:
- Effects of Carrier on Disposition and Antitumor Activity of Intraperitoneal PaclitaxelPharmaceutical Research, 2007
- Tumor Priming Enhances Delivery and Efficacy of NanomedicinesThe Journal of pharmacology and experimental therapeutics, 2007
- Health-Related Quality of Life During and After Intraperitoneal Versus Intravenous Chemotherapy for Optimally Debulked Ovarian Cancer: A Gynecologic Oncology Group StudyJournal of Clinical Oncology, 2007
- A phase I trial of intraperitoneal sustained-release paclitaxel microspheres (Paclimer®) in recurrent ovarian cancer: A Gynecologic Oncology Group studyGynecologic Oncology, 2006
- Intraperitoneal Chemotherapy of Ovarian Cancer: A Review, With a Focus on Practical Aspects of TreatmentJournal of Clinical Oncology, 2006
- Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneumJournal of Biomedical Materials Research Part A, 2006
- Time-and concentration-dependent penetration of doxorubicin in prostate tumorsAAPS PharmSci, 2001
- Intraperitoneal Cisplatin plus Intravenous Cyclophosphamide versus Intravenous Cisplatin plus Intravenous Cyclophosphamide for Stage III Ovarian CancerThe New England Journal of Medicine, 1996
- Evidence Supporting the Superiority of Intraperitoneal Cisplatin Compared to Intraperitoneal Carboplatin for Salvage Therapy of Small-Volume Residual Ovarian CancerGynecologic Oncology, 1993
- Biodegradation of and tissue reaction to 50:50 poly(DL‐lactide‐co‐glycolide) microcapsulesJournal of Biomedical Materials Research, 1985