Facile Mixing of Phospholipids Promotes Self-Assembly of Low-Molecular-Weight Biodegradable Block Co-Polymers into Functional Vesicular Architectures.

Amit Kumar Khan,Bo Liedberg,James C S Ho,Susmita Roy,Madhavan Nallani

doi:10.3390/polym12040979

Abstract

In this work, we have used low-molecular-weight (PEG12-b-PCL6, PEG12-b-PCL9 or PEG16-b-PLA38; MW, 1.25–3.45 kDa) biodegradable block co-polymers to construct nano- and micron-scaled hybrid (polymer/lipid) vesicles, by solvent dispersion and electroformation methods, respectively. The hybrid vesicles exhibit physical properties (size, bilayer thickness and small molecule encapsulation) of a vesicular boundary, confirmed by cryogenic transmission electron microscopy, calcein leakage assay and dynamic light scattering. Importantly, we find that these low MW polymers, on their own, do not self-assemble into polymersomes at nano and micron scales. Using giant unilamellar vesicles (GUVs) model, their surface topographies are homogeneous, independent of cholesterol, suggesting more energetically favorable mixing of lipid and polymer. Despite this mixed topography with a bilayer thickness similar to that of a lipid bilayer, variation in surface topology is demonstrated using the interfacial sensitive phospholipase A2 (sPLA2). The biodegradable hybrid vesicles are less sensitive to the phospholipase digestion, reminiscent of PEGylated vesicles, and the degree of sensitivity is polymer-dependent, implying that the nano-scale surface topology can further be tuned by its chemical composition. Our results reveal and emphasize the role of phospholipids in promoting low MW polymers for spontaneous vesicular self-assembly, generating a functional hybrid lipid-polymer interface.

Highlights

Nature has evolved a self-assembled lipid membrane that encloses a crowded pool of proteinaceous constituents, allowing the selective exchange of information between the intracellular milieu and the extracellular environment [1,2]
Self-assembly of block copolymers (BCPs) into vesicles is mainly defined by their fhydrophilic and εh, the monomer’s effective interaction energy with the bulk solution [16,37]
We have prepared nano- and micron-scale hybrid lipid-polymer vesicles consisting of phospholipids and low MW biodegradable BCPs

Summary

Introduction

Nature has evolved a self-assembled lipid membrane that encloses a crowded pool of proteinaceous constituents, allowing the selective exchange of information between the intracellular milieu and the extracellular environment [1,2]. Polymersomes, on the other hand, show higher mechanical and chemical stability and biofunctionality [16] They suffer from lower biocompatibility and, have not been as widely applied as the lipid counterpart. A mixed system allows one to obtain a vehicle that is robust (mechanically stable with low permeability) [17], chemically versatile (possibility to be tuned and functionalized), and biocompatible, providing a promising avenue for diverse applications. This has been explored in recent years using different di- and tri-block copolymers, in combination with lipids forming fluid or gel phases [13,18,19]

Methods

Results

Conclusion