Microfluidic encapsulation of SN-38 in block copolymer nanoparticles: effect of hydrophobic block composition on loading and release properties

A gas-liquid microfluidic reactor was used to prepare polymer nanoparticles (PNPs) containing the drug 7-ethyl-10- hydroxy camptothecin (SN-38) from a series of poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) (P(MCL-co-CL)- b-PEO) amphiphilic block copolymers with variable MCL content in the hydrophobic block. All three copolymers formed spheres with 20 nm core diameters by TEM, although some rigid rod-like aggregates were also formed by the PMCL-50 and PMCL-75 copolymers. SN-38 encapsulation efficiencies (EE = 2.7%-3.0%) and loading levels (DL = 2.0%-2.9%) were similar for the three copolymers. In vitro release kinetics became significantly slower as the MCL content increased, with release half times increasing monotonically from 3.4 to 6.2 h as the MCL content of the hydrophobic block increased from 50% to 100%. The ability to systematically tune release half times via controlled variation in the hydrophobic block composition, while maintaining constant PNP size and loading levels, represents an intriguing chemical handle for the optimization of SN-38 nanomedicines. (author)