Drug Delivery using Supercritical Carbon Dioxide-Assisted Impregnation of Biocompatible Polymeric Implants

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In recent years controlled drug delivery using various biodegradable or biocompatible polymeric implants has generated increasing interests by impregnating the desired therapeutic agents for sustaining the drug effect for a prolong time.  Supercritical CO2 –assisted impregnation of a drug, a protein or a vaccine on a polymeric carrier obviates the drawbacks of the conventional processes, such as, solubility and recrystallization.  SC CO2 can penetrate and plasticize the polymeric matrix, thereby creating a path way for the transport of the large molecules with structural stability and thus tailoring the morphology of the carrier for impregnation of the SC CO2 soluble bioactive compounds.

In this process, the drug is first solubilized in SCCO2 and then CO2 plus drug is allowed to contact the polymer for impregnation of the drug.  Various parameters such as solubility of the drug in SCCO2, absorption of SCCO2 into the polymer, and affinity between drug and polymer can influence the drug loading process and may affect the properties of the drug loaded implant.  Numerous APIs (drugs, genes, or proteins) have been reported to be packed into various biocompatible polymeric implants (e.g.,PLA, PLGA, PCL, poly(methyl methacrylate) (PMMA), and others), biodegradable polymers (e.g., chitosan derivatives, and siliconebased copolymers) These implants have considerable mechanical strengths and have been envisioned for various biomedical applications, such as, ophthalmic, orthopedic stents, and other implantable medical devices to increase the bioavailability of the drugs.

The present project aims to investigate SC CO2 –assisted impregnation of two such polymers with pure and mixed drugs, analytically characterize them, and analyze the effects of operating pressure, temperature, drug concentration, depressurization rate, and the nature of the drug – polymer-CO2 interactions on the loading and dissolution of the drugs from the SC CO2 processed polymeric matrix, both experimentally and by mathematical modeling.

 

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