Design of diffusion-controlled drug delivery devices for controlled release of Paclitaxel.

Controlled drug delivery devices were predicted in a reverse engineering framework for the controlled release of Paclitaxel, an anti-cancer drug, widely used in the treatment of solid tumors. Using quantitative structure-property relationship models for mutual diffusion coefficients of the drug in biocompatible and biodegradable polymers and partition coefficients of the drug between polymers and blood, a framework was developed to predict optimal drug delivery devices for desired dosage regimens. The validation of the predicted mutual diffusion and partition coefficients using experimental data was reported in previous studies. Optimal design parameters along with selection of most appropriate polymers suitable for different dosage regimens, selected based on current clinical practice, were predicted for maximum bioavailability of the drug while maintaining the released drug concentration in blood within the therapeutic range. Reservoir and monolithic type of diffusion-controlled drug delivery devices of different shapes and sizes were predicted with different initial drug loadings and bioavailability for different dosage regimens. The effects of the released Paclitaxel from these devices on the tumor growth were also modeled using a previously reported mathematical pharmacokinetic-pharmacodynamic model. The proposed approach can easily be used to design other diffusion-controlled drug delivery devices.

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