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

Abstract

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.

Hierarchical Self-Assembly Route to “Polyplex-in-Hydrophobic-Core” Micelles for Gene Delivery

“…The final particles following removal of unencapsulated pDNA are designated PIHC micelles. Recent work from our group has demonstrated significant effects of on-chip shear forces in two-phase microfluidic reactors such as the one applied here (Figure ) on the structure and function of polymer-based materials for nanomedicine materials. − Therefore, we were interested in comparing PIHC micelle samples prepared by the bulk and microfluidic SA2 processes in terms of their encapsulation efficiencies (EE), size distributions, and morphologies.…”