Development of PLGA-based drug encapsulation, delivery, and release system
Date Issued
2014
Date
2014
Author(s)
Yang, Kai-Hsiang
Abstract
In our study, a PLGA-based drug delivery system was developed. PLGA (Poly Lactic-co-Glycolic Acid) microsphere having the ability to carry hydrophobic drugs was fabricated to achieve the goals of protecting drugs, sustaining drug release and controlling drug release in vivo. Alginate, a hydrophilic polymer, was combined with PLGA microsphere to enhance its functions. Alginate-PLGA microsphere can simultaneously carry hydrophilic and hydrophobic drugs and release drugs in different stages.
We combined droplet-based microfluidics and solvent evaporation to fabricate size-controllable and monodisperse PLGA microspheres. The mean diameter was 34 μm and coefficient of variance was 6.39%. Size of PLGA microsphere was regulated by concentration of PLGA and diameter of droplet produced by microfluidic device. We chose curcumin as the model drug, examining possibility of carrying hydrophobic drugs. Curcumin was successfully covered in PLGA microspheres. However, the difference of solubility between PLGA and curcumin caused the space distribution of curcumin in PLGA microsphere was non-uniform. We seeded H9c3 cells with curcumin-PLGA microspheres. The cells had a tendency to grow nearby the microspheres and exhibited no significant cytotoxity. On this basis, we could develop a strategy to decreased cardiotoxity induced by chemotherapeutic drugs and synergistic interaction of chemicals and curcumin-PLGA microsphere in cancer cells. In order to add a factor of influencing drug release in vivo, we chose sodium hydrocarbonate as porogen to make porous PLGA microsphere. The higher concentration of sodium hydrocoarbinate caused the higher expansion (100 μm) of porous PLGA microsphere and the numbers of pores and their size were also larger. Numbers and size could effectively control drug release rate. On the basis of porous microsphere, alginate was filled in the pores to form alginate-PLGA microsphere. Hydrophilic and hydrophobic dyes were replaced as drugs. Alginate-PLGA microsphere could simultaneously carry hydrophilic and hydrophobic dyes and had the ability to release hydrophilic dye (blue) in the first stage and hydrophobic dye (red) in the second stage. It proved that alginate-PLGA microsphere had potential to release the drugs in different stages.
We combined droplet-based microfluidics and solvent evaporation to fabricate size-controllable and monodisperse PLGA microspheres. The mean diameter was 34 μm and coefficient of variance was 6.39%. Size of PLGA microsphere was regulated by concentration of PLGA and diameter of droplet produced by microfluidic device. We chose curcumin as the model drug, examining possibility of carrying hydrophobic drugs. Curcumin was successfully covered in PLGA microspheres. However, the difference of solubility between PLGA and curcumin caused the space distribution of curcumin in PLGA microsphere was non-uniform. We seeded H9c3 cells with curcumin-PLGA microspheres. The cells had a tendency to grow nearby the microspheres and exhibited no significant cytotoxity. On this basis, we could develop a strategy to decreased cardiotoxity induced by chemotherapeutic drugs and synergistic interaction of chemicals and curcumin-PLGA microsphere in cancer cells. In order to add a factor of influencing drug release in vivo, we chose sodium hydrocarbonate as porogen to make porous PLGA microsphere. The higher concentration of sodium hydrocoarbinate caused the higher expansion (100 μm) of porous PLGA microsphere and the numbers of pores and their size were also larger. Numbers and size could effectively control drug release rate. On the basis of porous microsphere, alginate was filled in the pores to form alginate-PLGA microsphere. Hydrophilic and hydrophobic dyes were replaced as drugs. Alginate-PLGA microsphere could simultaneously carry hydrophilic and hydrophobic dyes and had the ability to release hydrophilic dye (blue) in the first stage and hydrophobic dye (red) in the second stage. It proved that alginate-PLGA microsphere had potential to release the drugs in different stages.
Subjects
PLGA(聚乳酸甘醇酸)
微流體系統
薑黃素
微米藥球
SDGs
Type
thesis
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