Monodispersed Sirolimus-Loaded PLGA Microspheres with a Controlled Degree of Drug–Polymer Phase Separation for Drug-Coated Implantable Medical Devices and Subcutaneous Injection

Abstract

Monodispersed sirolimus (SRL)-loaded poly(lacticco-glycolic acid) microspheres with a diameter of 1.8, 3.8, and 8.5 μm 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 μm 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 °C 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.

Biodegradable AZ91 magnesium alloy/sirolimus/poly D, L‐lactic‐co‐glycolic acid‐based substrate for cardiovascular device application

“…The weak C‐H bond and fragrance ring are shown by the peak around 1687 cm −1 . Similar to this, peaks at 1089, 1015, and 693 cm −1 , respectively, were attributed to strong OH bending (compound class: carboxylic acid), CC alkene, and strong CO solid stretching 75 . Therefore, the FTIR spectra confirmed the essential role of NaOH in initiating bonding between surface, sirolimus molecule and PLGA coating.…”

Microstructure Formation and Characterization of Long-Acting Injectable Microspheres: The Gateway to Fully Controlled Drug Release Pattern

“…29,85 Compared with mechanically-cut microspheres, FIB can provide higher accuracy and precision, thus obtaining a clean and artifact-free cross section for high-resolution SEM imaging. 8,98 For subsequent SEM imaging, the beam emitted by the electron gun passes through a pair of objective lens and aperture to form an extremely narrow high-energy electron beam, which is further focused on the sample surface through objective lens. Various signals are excited through the interaction between the beam and the sample, and each of those signals could be collected, amplified and re-imaged by a specific detector to achieve the purpose of characterization of the material microstructure.…”

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres

“…[18][19][20] Besides, a series of long-term sustained release preparation have been reported, 21,22) among which the most common is drug-loaded PLGA microspheres, and their properties such as drug loading, encapsulation rate and drug release rate have been studied in detail. [23][24][25] PLGA, an aliphatic polyester, has been applied in clinical practice due to its good biocompatibility and biodegradability 26,27) and is one of the most successfully developed biodegradable polymers. Recently, PLGA microsphere delivery system is widely used in anti-tumor, 28) anti-inflammatory 29) and anti-bacterial 30) treatment.…”