Microfluidic Preparation of Microparticles Capable of Sustained Release of Nanoparticles

作者：Zhang, Hou-bing; Tian, Tai-yu; Feng, Qi; He, Xin-yu; Du, Xiao-jiao; Dong, Hua; Xiong, Meng-hua; Yan, Li-feng^*; Wang, Jun^*

来源：ACTA POLYMERICA SINICA, 2020, 51(11): 1240-1247.

DOI：10.11777/j.issn1000-3304.2020.20090

• Nanoparticle release
• Microparticles
• Microfluidics
• Controlled preparation
• Biodegradable polymer

Microparticles that are capable of sustained release of nanoparticles have been widely used as drug delivery carriers for pulmonary delivery, oral delivery and intratumoral delivery, with the advantages of local retention and sustained release of nanoparticles to promote tissue penetration and cellular uptake of drugs. Herein, a strategy to prepare microparticles capable of sustainably releasing nanoparticles by droplet-based microfluidic approach was reported. Biodegradable amphiphilic polymers PCL-Dlinkm-PAMAMs were first synthesized through the reaction of 2-propionic-3-methylmaleic anhydride (CDM) modified poly(epsilon-caprolactone) (PCL) and poly(amidoamine) dendrimer (PAMAM), generating labile amide bonds. By tuning the feed ratio, a series of amphiphilic polymers with different PCL conjugates (PCL-Dlinkm)(n)-PAMAM (n = 1 - 5) were synthesized. With droplet-based microfluidic approach, these polymers were assembled into microparticles by the hydrophobic interaction of PCL segments. The size of microparticles was well-controlled by adjusting the ratio of flow rates of continuous phase and dispersed phase. It was found that regularly spherical microparticles (imCluster) were formed only when more than two PCL segments were conjugated on the amphiphilic polymer. These imCluster could sustainably release PAMAM nanoparticles after the cleavage of amide bonds in the aqueous solution. This study developed a class of microparticles with controlled size and capability of sustained release of nanoparticles.

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