Polilactofate microspheres for Paclitaxel delivery to central nervous system malignancies.

Abstract

PURPOSE:

The purpose of this study was to demonstrate that surgically implanted, controlled-release, biodegradable polilactofate microspheres (Paclimer) can be used safely to bypass the blood-brain barrier and deliver paclitaxel to malignant brain tumors.

EXPERIMENTAL DESIGN:

The rate of paclitaxel release from Paclimer microspheres submerged in PBS was measured in vitro by high-performance liquid chromatography. In vivo studies of Paclimer were performed as intracranial implants in Fischer 344 rats in the presence or absence of 9L gliosarcoma. Mantel-Cox statistics were used to assess the efficacy of Paclimer at extending survival of tumor-bearing animals compared with control implants. Paclimer implants tagged with [(3)H]paclitaxel were used to measure biodistribution of paclitaxel from the Paclimer implant.

RESULTS:

Paclimer released paclitaxel at a constant rate for up to 3 months in vitro. In vivo, Paclimer implants placed intracranially in rats released active drug for up to 30 days after implantation and doubled the median survival of rats bearing established 9L gliosarcomas (median survival of paclitaxel-treated animals = 35 days; median survival of control-treated animal = 16 days; P < 0.0001). Active drug was distributed throughout the rat brain based on liquid scintillation counting and TLC. Rats implanted with Paclimer demonstrated no overt signs of neurotoxicity and exhibited local cytopathological changes consistent with exposure to an antimicrotubule agent.

CONCLUSIONS:

Paclimer extends survival in a rodent model of glioma with minimal morbidity and optimal pharmacokinetics.

• Authors: Khan W Li, Wenbin Dang, Betty M Tyler, Greg Troiano, Tarik Tihan, Henry Brem, Kevin A Walter
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 9 Pg. 3441-7 (Aug 15 2003) ISSN: 1078-0432 [Print] United States
• PMID: 12960135 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biocompatible Materials
• polilactofate
• Paclitaxel

Topics

• Animals
• Biocompatible Materials (pharmacokinetics)
• Blood-Brain Barrier
• Cell Line, Tumor
• Central Nervous System Neoplasms (drug therapy)
• Chromatography, High Pressure Liquid
• Drug Delivery Systems
• Glioma (drug therapy)
• Inflammation
• Male
• Microspheres
• Paclitaxel (administration & dosage, chemistry)
• Proportional Hazards Models
• Rats
• Rats, Inbred F344
• Time Factors