期刊
ACS APPLIED BIO MATERIALS
卷 5, 期 8, 页码 3766-3777出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.2c00319
关键词
step microfluidic emulsification; drug delivery; drug-eluting medical devices; biodegradable polymer; poly(lactic-co-glycolic acid); controlled drug release
资金
- EPSRC National Productivity Investment Fund of the United Kingdom [EP/R512576/1]
- Med-Alliance Switzerland
- Bridge UK-JSPS Fellowship [BR130302]
Monodispersed sirolimus-loaded poly(lactic-co-glycolic acid) microspheres were successfully produced using high-throughput microfluidic technology. As the drug loading increased, the morphology of the particles evolved from homogeneous microspheres to patchy particles and eventually to Janus particles with fully segregated drug and polymer regions.
Monodispersed sirolimus (SRL)-loaded poly(lactic-co-glycolic acid) microspheres with a diameter of 1.8, 3.8, and 8.5 mu m were produced by high-throughput microfluidic step emulsification-solvent evaporation using single crystal silicon chips consisted of 540-1710 terraced microchannels with a depth of 2, 4, or 5 mu m arranged in 10 parallel arrays. Uniform sized droplets were generated over 25 h across all channels. Nearly 15% of the total drug was released by the initial burst release during an accelerated drug release testing performed at 37 ? using a hydrotropic solution containing 5.8 M N,N-diethylnicotinamide. After 24 h, 71% of the drug was still entrapped in the particles. The internal morphology of microspheres was investigated by fluorescence microscopy using Nile red as a selective fluorescent stain with higher binding affinity toward SRL. By increasing the drug loading from 33 to 50 wt %, the particle morphology evolved from homogeneous microspheres, in which the drug and polymer were perfectly mixed, to patchy particles, with amorphous drug patches embedded within a polymer matrix to anisotropic patchy Janus particles. Janus particles with fully segregated drug and polymer regions were achieved by pre-saturating the aqueous phase with the organic solvent, which decreased the rate of solvent evaporation and allowed enough time for complete phase separation. This approach to manufacturing drug-loaded monodisperse microparticles can enable the development of more effective implantable drug-delivery devices and improved methods for subcutaneous drug administration, which can lead to better therapeutic treatments.
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