Computer simulation of the delivery of etanidazole to brain tumor from PLGA wafers: comparison between linear and double burst release systems.

This paper presents the computer simulation results on the delivery of Etanidazole (radiosensitizer) to the brain tumor and examines several factors affecting the delivery. The simulation consists of a 3D model of tumor with poly(lactide-co-glycolide) (PLGA) wafers with 1% Etanidazole loading implanted in the resected cavity. A zero-order release device will produce a concentration profile in the tumor which increases with time until the drug in the carrier is depleted. This causes toxicity complications during the later stages of drug treatment. However, for wafers of similar loading, such release results in a higher drug penetration depth and therapeutic index as compared to the double drug burst profile. The numerical accuracy of the model was verified by the similar results obtained in the two-dimensional and three-dimensional models.

[1]  C. Coleman,et al.  Relationship between the neurotoxicity of the hypoxic cell radiosensitizer SR 2508 and the pharmacokinetic profile. , 1987, Cancer research.

[2]  Jian Li,et al.  Three-dimensional simulation of IgG delivery to tumors , 1998 .

[3]  J. Li,et al.  The delivery of BCNU to brain tumors. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[4]  S. Piantadosi,et al.  Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas , 1995, The Lancet.

[5]  B Horwitz,et al.  A mathematical model for vasogenic brain edema. , 1978, Advances in neurology.

[6]  R. Tamargo,et al.  Interstitial chemotherapy of the 9L gliosarcoma: controlled release polymers for drug delivery in the brain. , 1993, Cancer research.

[7]  Sampath,et al.  Implantable Slow-Release Chemotherapeutic Polymers for the Treatment of Malignant Brain Tumors. , 1998, Cancer control : journal of the Moffitt Cancer Center.

[8]  C E LUMSDEN,et al.  The significance of the tissue pressure of normal testicular and of neoplastic (Brown-Pearce carcinoma) tissue in the rabbit. , 1950, The Journal of pathology and bacteriology.

[9]  K. Hwang,et al.  Stress distribution in a confined wet cake in the compression—permeability cell and its application , 1998 .

[10]  W. Mark Saltzman,et al.  Chemotherapeutic Drugs Released from Polymers: Distribution of 1,3-bis(2-chloroethyl)-l-nitrosourea in the Rat Brain , 1996, Pharmaceutical Research.

[11]  S. Lehnert,et al.  Radiosensitization of a mouse tumor model by sustained intra-tumoral release of etanidazole and tirapazamine using a biodegradable polymer implant device. , 1999, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  S Torquato,et al.  Cellular automaton of idealized brain tumor growth dynamics. , 2000, Bio Systems.

[13]  Chi‐Hwa Wang,et al.  PEG modulated release of etanidazole from implantable PLGA/PDLA discs. , 2002, Biomaterials.

[14]  R. Wooding.  Steady state free thermal convection of liquid in a saturated permeable medium , 1957, Journal of Fluid Mechanics.

[15]  S Torquato,et al.  Simulated brain tumor growth dynamics using a three-dimensional cellular automaton. , 2000, Journal of theoretical biology.

[16]  R K Jain,et al.  Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection. , 1989, Microvascular research.