Curvature-Coupled Hydration of Semicrystalline Polymer Amphiphiles Yields flexible Worm Micelles but Favors Rigid Vesicles: Polycaprolactone-Based Block Copolymers

Abstract

Crystallization processes are in general sensitive to detailed conditions, but our present understanding of underlying mechanisms is insufficient. A crystallizable chain within a diblock copolymer assembly is expected to couple curvature to crystallization and thereby impact rigidity as well as preferred morphology, but the effects on dispersed phases have remained unclear. The hydrophobic polymer polycaprolactone (PCL) is semi-crystalline in bulk (T m = 60°C) and is shown here to generate flexible worm micelles or rigid vesicles in water from several dozen polyethyleneoxide-based diblocks (PEO-PCL). Despite the fact that `worms' have a mean curvature between that of vesicles and spherical micelles, `worms' are seen only within a narrow, process-dependent wedge of morphological phase space that is deep within the vesicle phase. Fluorescence imaging shows worms are predominantly in one of two states -either entirely flexible with dynamic thermal undulations or fully rigid; only a few worms appear rigid at room temperature (T << T m ), indicating suppression of crystallization by both curvature and PCL hydration. Worm rigidification, which depends on molecular weight, is also prevented by copolymerization of caprolactone with just 10% racemic lactide that otherwise has little impact on bulk crystallinity. In contrast to worms, vesicles of PEO-PCL are always rigid and typically leaky. Defects between crystallite domains induce dislocation-roughening with focal leakiness although select PEO-PCL -which classical surfactant arguments would predict make worms -yield vesicles that retain encapsulant and appear smooth, suggesting a gel or glassy state. Hydration in dispersion thus tends to selectively soften high curvature microphases.Keywords block copolymer; worm micelle; polymersome; crystallinity Corresponding: discher@seas.upenn.edu. Supporting Information. Molecular details of all polymers synthesized, calculation of polymer distribution in assemblies, AFM and fluorescence microscopy images, DLS and dye encapsulation studies, movies of worm micelles, persistence length measurement of worm micelles, procedure for measurement of contour lengths, and phase contrast images of OCL (2, 13.5) can be found in Supporting Information. Supporting Information is available free of charge on the internet at

Biomimetic materials in regenerative medicine

“…1.10 ), similar to that reported for both PLLA and PCL in in vitro systems (Rajagopal et al , 2010, Andreopoulos et al , 1999. However, variable wall thickness, as well as a convoluted external surface of the vessel profi les, occurred with both biomaterials, and calibre patency progressively decreased at the arteriolar/venular and capillary levels.…”

Advances in drug delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers

“…The formation of original and stable micelles can be induced by restricted polymer chains mobility during the formulation process thanks to the use of non-linear block copolymers [160,161]. Indeed, Liu and co-workers, and Li and co-workers reported the use of star-shaped copolymers consisting of multiple adamantyl end-capped PHB anchored to a central star-shaped PEG (average of 6 or 7 arms; sPEG) block as potential DDS (Figure 4).…”

Polymeric Micelles Possessing Polyethyleneglycol as Outer Shell and Their Unique Behaviors in Accelerated Blood Clearance Phenomenon

“…Block copolymers containing PEG are prepared with polymerization of another monomer from a terminal of PEG. Two most commonly examined block copolymers, PEG-bpoly(amino acid) s 19) and PEG-b-polyesters, 25) are synthesized from a primary amino terminal and from a hydroxyl terminal of PEG, respectively. A high terminal functionality (100% is ideal) makes it possible to obtain a high purity of block copolymer.…”