The Relationships between Partition Coefficient and Size in Micelles of PLLA-PEG-PLLA Triblock Copolymers and Their Drug Release Experiments

• Main Authors: Si-Xian Li, 李思賢
• Other Authors: Shiaw-Guang Hu
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/07254848638991263295

碩士 === 國立臺灣科技大學 === 高分子系 === 97 === Poly(ethylene glycol)-Poly(L-lactide) (PEG-PLLA-PEG) triblock copolymers with PEG（The number average of molecular weight ＝4000 g/mol）and various PLLA length（monomer number from 149 to 478）were synthesized, and the critical micelle concentrations（CMC’s）, micellar radius and concentration of Vitamin K3 in the micelles for various copolymers were determined with fluorescence spectroscopy with pyrene probe, dynamic light scattering, and UV/Vis spectroscopy, respectively. It is found that CMC’s decrease with PLLA block length. The micellar radius and partition coefficient from the water phase to micelle increases with the PLLA length and micellar radius is proportional to the 0.46th power of PLLA block length, which fits the prediction by Halperin. We plot of the double logarithm of partition coefficient versus the logarithm of micellar radius, show that the scaling exponent is smaller for PLLA-PEG-PLLA than PLLA-MePEG diblock copolymers, due to the smaller enthalpy of micellization of PLLA-PEG-PLLA is smaller then PLLA-MePEG. The looping effect of PEG segment maybe affect the entropy of the micelle core, and the interfacial energy of triblock copolymer is smaller than diblock copolymer, making the scaling exponent of PLLA-PEG-PLLA triblock copolymer smaller. In the relationship between the logarithm of partition coefficient and the reciprocal of hydrophobic length, the slopes are related to the core-water interaction parameters and the interfacial energy between triblock or diblok copolymers and water phase. We use the same methods of analysis to evaluate exponents and slopes in various conductions and drugs in literature, and relate them to the interfacial free energy of the drugs from water to micelle phase as the extra factor. The concentrations of Vitamin K3 releasing from the micelles of PLLA-PEG-PLLA triblock copolymer were determined by UV/Visible spectroscopy in a time interval of one hour. In the initial stage, the slopes of plots of the fractional release (1-F) versus the time decrease with increasing the partition coefficient. The exponents between fractional release and dimensionless release time (π1) increases with dimensionless drug partition constant (π2). The exponents between (1-F) and π1 of Fick’s sphere model, Higuchi model, and the literature data dealing with the release of the 17β-estradiol from the micelles of PCL-PEO diblock copolymers, are affected by π2, and the same trend was also found in our experiments. When π2 is bigger, the release mechanism approaches closer to the constant rate release. The absolute value of exponent between (1-F) and π2 of our experiment is bigger than the absolute value of exponent in the literature, as a result that the π2 of our experiment is smaller than that in the literature. The saturated fractional release decrease with increasing the partition coefficient in our experiment, which can not fitted with the drug release model predicting the saturated fractional release of drug approaching to 1 at any dimensionless drug partition constant.