Multi-Scale Modeling of Polymer-Drug Interactions and their Impact on the Structural Evolutions in PLGA-Tetracycline Films
Mentor 1
Dr. Changsoo Kim
Location
Union Wisconsin Room
Start Date
29-4-2016 1:30 PM
End Date
29-4-2016 3:30 PM
Description
Poly(lactic/glycolic acid) (PLGA)-based polymers have been extensively investigated as promising carries to control the release rates for various types of pharmaceutical agents. In this study, we employed an atomistic molecular dynamics (MD) computation approach to quantifying the Flory-Huggins parameters between poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and tetracycline-HCl (TC-HCl) drugs, which can elucidate the thermodynamic stability and the interaction between drugs and PLGA polymers. Thermodynamic analysis regarding the miscibility and the stability of PLA, PGA, TC-HCl phases were then conducted in line with the experimental fabrication of polymer-drug films of two different copolymer ratio products, i.e., 50/50 (PLA/PGA ratio) and 75/25 PLGA samples. Meso-scale computations using phase-field method (PFM) were also conducted to predict the structural evolution of PLGA/TC-HCl systems using the calculated Flory-Huggins parameters. The obtained results indicate that for the independent constituents of PLA and PGA, mixing is not thermodynamically favorable for compositions in the range of 10/90 to 90/10 wt% PLA/PGA. Similarly, Flory-Huggins analysis of PLA/TC and PGA/TC 15 and 45wt% polymer blends respectively indicates that PLA will experience poor miscibility with TC in contrast to PGA due to lacking asymmetrical methyl groups and a lower degree of molecule hydrophilicity. The structural morphology of the systems presented was highly dependent upon the thermodynamic interactions between the polymer and drug phases. Using atomic force microscopy (AFM), scans of 50/50 and 75/25 PLGA films were then found to portray phase-separated drug particle and polymer matrix structures. Experimental observation of overall size and distribution of embedded drug particles were found to be in line with obtained MD computational data, and these variations in size are thought to potentially influence resulting drug release kinetics from PLGA-TC coatings as larger drug particle sizes typically dissolve less readily.
Multi-Scale Modeling of Polymer-Drug Interactions and their Impact on the Structural Evolutions in PLGA-Tetracycline Films
Union Wisconsin Room
Poly(lactic/glycolic acid) (PLGA)-based polymers have been extensively investigated as promising carries to control the release rates for various types of pharmaceutical agents. In this study, we employed an atomistic molecular dynamics (MD) computation approach to quantifying the Flory-Huggins parameters between poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and tetracycline-HCl (TC-HCl) drugs, which can elucidate the thermodynamic stability and the interaction between drugs and PLGA polymers. Thermodynamic analysis regarding the miscibility and the stability of PLA, PGA, TC-HCl phases were then conducted in line with the experimental fabrication of polymer-drug films of two different copolymer ratio products, i.e., 50/50 (PLA/PGA ratio) and 75/25 PLGA samples. Meso-scale computations using phase-field method (PFM) were also conducted to predict the structural evolution of PLGA/TC-HCl systems using the calculated Flory-Huggins parameters. The obtained results indicate that for the independent constituents of PLA and PGA, mixing is not thermodynamically favorable for compositions in the range of 10/90 to 90/10 wt% PLA/PGA. Similarly, Flory-Huggins analysis of PLA/TC and PGA/TC 15 and 45wt% polymer blends respectively indicates that PLA will experience poor miscibility with TC in contrast to PGA due to lacking asymmetrical methyl groups and a lower degree of molecule hydrophilicity. The structural morphology of the systems presented was highly dependent upon the thermodynamic interactions between the polymer and drug phases. Using atomic force microscopy (AFM), scans of 50/50 and 75/25 PLGA films were then found to portray phase-separated drug particle and polymer matrix structures. Experimental observation of overall size and distribution of embedded drug particles were found to be in line with obtained MD computational data, and these variations in size are thought to potentially influence resulting drug release kinetics from PLGA-TC coatings as larger drug particle sizes typically dissolve less readily.
