Testing the Vesicular Morphology to Destruction: Birth and Death of Diblock Copolymer Vesicles Prepared via Polymerization-Induced Self-Assembly

Abstract

Small angle X-ray scattering (SAXS), electrospray ionization charge detection mass spectrometry (CD-MS), dynamic light scattering (DLS), and transmission electron microscopy (TEM) are used to characterize poly(glycerol monomethacrylate)55-poly(2-hydroxypropyl methacrylate)x (G55-Hx) vesicles prepared by polymerization-induced self-assembly (PISA) using a reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization formulation. A G55 chain transfer agent is utilized to prepare a series of G55-Hx diblock copolymers, where the mean degree of polymerization (DP) of the membrane-forming block (x) is varied from 200 to 2000. TEM confirms that vesicles with progressively thicker membranes are produced for x = 200–1000, while SAXS indicates a gradual reduction in mean aggregation number for higher x values, which is consistent with CD-MS studies. Both DLS and SAXS studies indicate minimal change in the overall vesicle diameter between x = 400 and 800. Fitting SAXS patterns to a vesicle model enables calculation of the membrane thickness, degree of hydration of the membrane, and the mean vesicle aggregation number. The membrane thickness increases at higher x values, hence the vesicle lumen must become smaller if the external vesicle dimensions remain constant. Geometric considerations indicate that this growth mechanism lowers the total vesicle interfacial area and hence reduces the free energy of the system. However, it also inevitably leads to gradual ingress of the encapsulated water molecules into the vesicle membrane, as confirmed by SAXS analysis. Ultimately, the highly plasticized membranes become insufficiently hydrophobic to stabilize the vesicle morphology when x exceeds 1000, thus this PISA growth mechanism ultimately leads to vesicle “death”.

A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly

“…As the DP of the core-forming PHPMA block increases, the vesicle membrane thickens, but the outer vesicle diameter is conserved, which leads to a gradual reduction in the vesicle lumen volume. 140 Geometric considerations confirm that this is actually the only mechanism by which the growing vesicles can minimize their total interfacial area and hence their free energy. Moreover, this mechanism places an important constraint on vesicle growth.…”

“…The exception is PGMA 55 –PGMA 1500 , which has a nonvesicular morphology as judged by TEM studies. Reproduced with permission from ref (140). …”

Self-assembly of thermo and light responsive amphiphilic linear dendritic block copolymers

“…In a first approach, this type of scattering is compatible with the presence of the vesicle observed by TEM. [17] [18] Due to the limited q range of the experiment, the scattering curve could not be fitted properly. However, based on TEM, a globular shape of the scattering objects can be considered and, therefore, SAXS profiles can be analyzed by using the Guinier approach for globular objects.…”

A Vesicle‐to‐Worm Transition Provides a New High‐Temperature Oil Thickening Mechanism

“…Transmission electron microscopy (TEM) studies have shed new light on the nature of the worm‐to‐vesicle transition that can occur under these conditions, which proceeds via a “jellyfish” intermediate 10. PISA formulations have enabled the rational synthesis of low‐polydispersity vesicles using a binary mixture of two macro‐CTAs11 and the precise mechanism of vesicle growth during such syntheses has been recently elucidated 10a, 12…”