A Ｓtudy on the Microsphere Fabrication and Mass Transport Properties of Biodegradable Polymer Substrates

• Main Authors: Yung-Sheng Lin, 林永昇
• Other Authors: Ruey-Yug Tsay
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/60209591150160341625

博士 === 國立陽明大學 === 醫學工程研究所 === 93 === The transport of nutriments and metabolites between implanted biomaterials and living tissue plays an important role in the clinical applications of biomaterials. Therefore, the mass transfer in biomaterials is an essential issue to be studied. This study is aimed to explore the transport phenomenon in two widely-applied biodegradable biomaterials, i.e., reconstituted collagen matrices and polylactide. In the study of the molecular transport in a reconstituted collagen matrix, it is found that the fibrous structure in a collagen matrix of 2~15 g/ml in concentration applies little hindrance to the transport of molecules smaller than 10 nm. This consists with the predictions of the proposed Fiber Matrix Model. For the drug-loaded PLA microspheres, a liquid/liquid injection method is developed in this study to fabricate microspheres of uniform size. Light microscopy and SEM observations reveal that this process can improve the problems of wide range of particle size distribution and aggregation between microspheres commonly seen in traditional emulsion methods and successfully fabricate microspheres with uniform size and pore structure. Also, an extraction model is established to predict the solidification behavior of the dispersed droplets in column. The validity of this extraction model is verified by experimental data. For the drug release of microspheres, a generalized release model considering the effect of a finite dissolution rate and removing the pseudo-steady state assumption is established. This generalized model is validated by the comparisons between the analytical solutions, numerical solutions and solutions by traditional release models. Experimental release data reported in literatures confirm that the present model can be generally applied in various microsphere drug release systems. In developing the CLSM system of in-situ detecting drug concentration profiles in microspheres, this study focuses on correcting the artifact caused image blurring and light intensity decay with depths to gain precisely concentration profiles in microspheres. The Green’s function-based image blurring model developed in this study is tested by images taken for fluorescence solutions with different concentrations and depths. This model successfully improves the edge detection of the images. Analysis in sequent images of microspheres indicates that the curvature of the microsphere and the absorption of the PLA substrate have very limited influences on the detection of concentration profiles. It is shown that image blurring is the major cause in affecting the accuracy of the detection.