Microfluidic-assisted nanoprecipitation of (PEGylated) poly (D,L-lactic acid-co-caprolactone): Effect of macromolecular and microfluidic parameters on particle size and paclitaxel encapsulation

Enrique Lallana-Ozores, Roberto Donno, Davide Magri, Katie Barker, Zahid Nazir, Kevin Treacher, Margaret Lawrence, Marianne Ashford, Nicola Tirelli

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Abstract

In this work we evaluate the effect of polymer composition and architecture of (PEGylated) polyesters on particle size and paclitaxel (PTX) loading for particles manufactured via microfluidic-assisted, continuous-flow nano-precipitation using two microfluidic chips with different geometries and mixing principles.
We have prepared poly (D, L-lactic acid-co-caprolactone) (PLCL) from ring-opening polymerization (ROP) of LA and CL mixtures and different (macro) initiators (namely, 1-dodecanol, a MeO-PEG-OH, and a 4-armed star PEG-OH), rendering polyesters that vary in monomer composition (i.e. LA/CL ratios) and architecture (i.e. linear vs 4-armed star). Continuous-flow nanoprecipitation was assayed using two microfluidic chips: a cross-flow chip with a X-shaped mixing junction (2D laminar flow focusing) and a micromixer featuring a Y-shaped mixing junction and a split and recombine path (2D laminar flow focusing convinced with stream lamination for faster mixing). Nanoparticle formulations were produced with Z-average sizes in the range of 30-160 nm, although size selectivity could be seen for different polymer/chip combinations; for instance, smaller particles were obtained with Y-shaped micromixer (30-120 nm), specially for the PEGylated polyesters (30-50 nm), whereas the cross-flow chip systematically produced larger particles (80-160 nm). Loading of the anti-cancer drug paclitaxel (PTX) was also heavily influenced not only by the nature of the polyester, but also by the geometry of the microfluidic chip; higher drug loadings were obtained with the cross-flow reactor and the star block copolymers. Finally, decreasing the LA/CL ratio generally had a positive effect on drug loading.
Original languageEnglish
Pages (from-to)530-539
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume548
Issue number1
Early online date17 Jul 2018
DOIs
Publication statusPublished - Sept 2018

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