Synthesis, Self-Assembly, and Drug Delivery Characteristics of Poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) Copolymers with Variable Compositions of Hydrophobic Blocks: Combining Chemistry and Microfluidic Processing for Polymeric Nanomedicines

Abstract

The synthesis, characterization, and self-assembly of a series of biocompatible poly(methyl caprolactone-co-caprolactone)-b-poly(ethylene oxide) amphiphilic block copolymers with variable MCL contents in the hydrophobic block are described. Self-assembly gives rise to polymeric nanoparticles (PNPs) with hydrophobic cores that decrease in crystallinity as the MCL content increases, and their morphologies and sizes show nonmonotonic trends with MCL content. PNPs loaded with the anticancer drug paclitaxel (PAX) give rise to in vitro PAX release rates and MCF-7 GI50 (50% growth inhibition concentration) values that decrease as the MCL content increases. We also show for selected copolymers that microfluidic manufacturing at a variable flow rate enables further control of PAX release rates and enhances MCF-7 antiproliferation potency. These results indicate that more effective and specific drug delivery PNPs are possible through tangential efforts combining polymer synthesis and microfluidic manufacturing.

Emerging applications for living crystallization-driven self-assembly

“…Over the past two decades, studies of the CDSA of BCPs with a crystallizable core-forming block in selective solvents have expanded dramatically. CDSA has been employed to fabricate mainly cylindrical and/or platelet micelles based on crystalline (or in some cases liquid crystalline) cores of PFDMS, 31,[34][35][36] poly(ferrocenylmethylsilane) (PFMS), 37 poly(ferrocenyldiethylsilane) (PFDES), 38 poly(ferrocenyldimethylgermane) (PFDMG), 39 other polymetallocenes, 40,41 poly(L-lactic acid) (PLLA), [42][43][44][45][46][47][48] polycaprolactone (PCL), 49,50,59,60,[51][52][53][54][55][56][57][58] PCL/PLLA copolymers, 61 polycarbonate, 62 poly(ethylene oxide/glycol) (PEO/PEG), [63][64][65] poly(pdioxanone) (PPDO), [66][67][68] polyethylene (PE), 69,70,[79][80][81][82][83][71][72][73][74]…”

Catalytic Activity of Various β‐Diketiminate Zinc Complexes toward the Ring‐Opening Polymerization of Caprolactone and Derivatives

“…Their activity and selectivity in the ROP of CL have been studied and compared with the activity of the known 1,4‐phenylene bridged bis( β ‐diketiminate) and the related mononuclear β ‐diketiminate zinc complex. Furthermore, the efficiency of the catalysts was also investigated for the polymerization of the CL derivatives ε ‐phenyl‐ ε ‐caprolactone (phCL) [ 67,68 ] and ε ‐methyl‐ ε ‐caprolactone (meCL) [ 69,70 ] that has been insufficiently studied till now.…”

Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties

“…The substrate layer was then permanently bonded to the base of the microfluidic reactor (channel layer) after both components were exposed to oxygen plasma for 45 s. The resulting reactor (Figure 1) has a set channel depth of 150 μm and consists of a sinusoidal mixing channel 100 μm wide and a sinusoidal processing channel 200 μm wide, identical to the reactor described in previous publications from our group. [24][25][26][27][28][29][30] Flow Delivery and Control. Pressure-driven flow of liquids to the reactor inlet was provided using 1 mL gastight syringes (Hamilton, Reno, NV) mounted on syringe pumps (Harvard Apparatus, Holliston, MA).…”

“…Our group has applied a two-phase, gas-liquid microfluidic platform for the manufacturing of PNP nanomaterials of controlled structure and properties. [18][19][20][21][22][23][24][25][26][27][28][29][30] In this reactor, counter-rotating vortices within the segmented liquid plugs enable fast on-chip mixing which triggers self-assembly and PNP formation. 18,19 Subsequent downstream processing of the resulting PNPs occurs in highshear "hot spots" as the formulation continues to move through the microchannels, analogous to industrial processing to modify the structure and properties of commodity polymer materials.…”

“…18,19 Subsequent downstream processing of the resulting PNPs occurs in highshear "hot spots" as the formulation continues to move through the microchannels, analogous to industrial processing to modify the structure and properties of commodity polymer materials. 18,19,29 Using our microfluidic platform for producing PNP delivery vehicles for the common anticancer drug paclitaxel (PAX), 24,26,27,30 we have shown that variation in the on-chip flow rate (which varies the maximum shear rate within the hot spots) provides a unique control handle on PNP sizes, morphologies, drug loading, release rates, and in vitro antiproliferation effects, independent of the formulation chemistry.…”