Microenvironment-Controlled Encapsulation (MiCE) Process: Effects of PLGA Concentration, Flow Rate, and Collection Method on Microcapsule Size and Morphology
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To evaluate the real-time effects of formulation and instrumental variables on microcapsule formation via natural jet segmentation, a new microencapsulation system termed the microenvironment-controlled encapsulation (MiCE) process was developed.
A modified flow cytometer nozzle hydrodynamically focuses an inner drug and outer polymer solution emanating from a coaxial needle assembly into a two-layer compound jet. Poly(lactic-co-glycolic acid) (PLGA) dissolved in a water-miscible organic solvent resulted in formation of reservoir-type microcapsules by interfacial phase separation induced at the boundary between the PLGA solution and aqueous sheath.
The MiCE process produced microcapsules with mean diameters ranging from 15–25 μm. The resultant microcapsule size distribution and number of drug cores existing within each microcapsule was largely influenced by the PLGA concentration and microcapsule collection method. Higher PLGA concentrations yielded higher mean diameters of single-core microcapsules. Higher drug solution flow rates increased the core size, while higher PLGA solution flow rates increased the PLGA film thickness.
The MiCE microencapsulation process allows effective monitoring and control of the instrumental parameters affecting microcapsule production. However, the microcapsule collection method in this process needs to be further optimized to obtain microcapsules with desired morphologies, precise membrane thicknesses, high encapsulation efficiencies, and tight size distributions.
Key wordsflow cytometry interfacial phase separation microcapsules PLGA Rayleigh breakup
This research project was funded in part by the NSF/Integrative Graduate Education and Research Traineeship Program on Therapeutic and Diagnostic Devices (grant DGE-99-72770) and the National Institutes of Health (grants GM67044 and EB003584).
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