Abstract

The approach of this NCDDG is to continue to develop biodegradable polymers that can be implanted at the site of the tumor and release effective drugs in a controlled manner as the polymer is degraded. Other programs are concerned with research related to providing new polymers and delivery systems for anti cancer drugs. Our program is aimed at development and is designed to provide polymer-drug combinations in optimal, reproducible formulations so that they can be tested in animals (preclinical); the effective formulations will be then scaled-up and extensively studied to be appropriate for human clinical trials (beyond the scope of this proposal). Through the previous NCDDG we have established the requirements for a suitable degradable implant to the brain by using the BCNU-polymer combination as representative. During the course of bringing this device through clinical trials many chemical, pharmaceutical, and pharmacological issues were investigated and the appropriate procedures have been established. These include: scale-up and quality control procedures for polymer manufacturing and drug incorporation; toxicology of the placebo and BCNU-loaded polymer under various conditions; and new polymers and various drugs were introduced to the program.
The specific aims of the current proposals are to 1) develop procedures for large scale production of clinical grade drug-polymer implants, focusing on the use of automated compression and injection molding processes, 2) develop methods to produce sufficient quantities of the new polymers and delivery systems developed,in other programs and supply of quality polymers and drug incorporated devices to the other programs, 3) Develop validated methods for the evaluation of the shelf life stability of anticancer polyanhydride delivery systems, 4) develop methods for studying Polymer-Drug interaction and protein stability in polymers, and 5) Determine the optimal gamma- irradiation sterilization dose for polyanhydride based delivery systems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19CA052857-09
Application #
6269447
Study Section
Project Start
1998-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Gabikian, Patrik; Tyler, Betty M; Zhang, Irma et al. (2014) Radiosensitization of malignant gliomas following intracranial delivery of paclitaxel biodegradable polymer microspheres. J Neurosurg 120:1078-85
Tyler, Betty; Wadsworth, Scott; Recinos, Violette et al. (2011) Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats. Neuro Oncol 13:700-9
Slager, Joram; Tyler, Betty; Shikanov, Ariella et al. (2009) Local controlled delivery of anti-neoplastic RNAse to the brain. Pharm Res 26:1838-46
Pradilla, Gustavo; Wang, Paul P; Gabikian, Patrik et al. (2006) Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. J Neurooncol 76:131-8
Sampath, Prakash; Rhines, Laurence D; DiMeco, Francesco et al. (2006) Interstitial docetaxel (taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma. J Neurooncol 80:9-17
Legnani, Federico G; Pradilla, Gustavo; Thai, Quoc-Anh et al. (2006) Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers. J Neurooncol 77:225-32
Li, Yawen; Ho Duc, Hong Linh; Tyler, Betty et al. (2005) In vivo delivery of BCNU from a MEMS device to a tumor model. J Control Release 106:138-45
Sorg, Brian S; Peltz, Cathryn D; Klitzman, Bruce et al. (2005) Method for improved accuracy in endogenous urea recovery marker calibrations for microdialysis in tumors. J Pharmacol Toxicol Methods 52:341-9
Li, Yawen; Shawgo, Rebecca S; Tyler, Betty et al. (2004) In vivo release from a drug delivery MEMS device. J Control Release 100:211-9
Grossi, Peter M; Ochiai, Hidenobu; Archer, Gary E et al. (2003) Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer. Clin Cancer Res 9:5514-20

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