Role of Membrane Features on the Permeability Behavior of Polymersomes and the Potential Impacts on Drug Encapsulation and Release

Abstract

Self-assembled bilayer structures such as those produced from amphiphilic block copolymers (polymersomes) are potentially useful in a wide array of applications including the production of artificial cells and organelles, nanoreactors, and delivery systems. These constructs are of important fundamental interest, and they are also frequently considered toward advances in bionanotechnology and nanomedicine. In this framework, membrane permeability is perhaps the most important property of such functional materials. Having in mind these considerations, we herein report the manufacturing of intrinsically permeable polymersomes produced using block copolymers comprising poly­[2-(diisopropylamino)-ethyl methacrylate] (PDPA) as the hydrophobic segment. Although being water insoluble at pH 7.4, its pK a(PDPA) ∼ 6.8 leads to the presence of a fraction of protonated amino groups close to the physiological pH, thus conducting the formation of relatively swollen hydrophobic segments. Rhodamine B-loaded vesicles demonstrated that this feature confers inherent permeability to the polymeric membrane, which can still be modulated to some extent by the solution pH. Indeed, even at higher pH values where the PDPA chains are fully deprotonated, the experiments demonstrate that the membranes remain permeable. While membrane permeability can be, for instance, regulated by introducing membrane proteins and DNA nanopores, examples of membrane-forming polymers with intrinsic permeability have been seldom reported so far, and the possibility to regulate the flow of chemicals in these compartments by tuning block copolymer features and ambient conditions is of due relevance. The permeable nature of PDPA membranes possibly applies to a wide array of small molecules, and these findings can in principle be translocated to a variety of disparate bio-related applications.

One‐pot preparation of nanoparticles via self‐assembly of sodium lignosulfonate and quaternary ammonium for controlled release of emamectin benzoate

“…A lower permeability would lead to a slower release. 49 As indicated by DLS, the size of both nanoparticles with and without EB decreased with increasing content of SL, which suggested a faster release as the results of a shorter distance that EB molecules had moved from internal region to the surface of the particle. However, the release of EB dropped from the nanoparticle of higher SL content, which indicated that the release was dominated by the absorption capacity of the vehicle.…”

Synthetic Cells Revisited: Artificial Cell Construction Using Polymeric Building Blocks

“…[86] Polymersome membranes usually exhibit low permeability unless they are assembled from selected polymers whose chemical nature results in an inherently porous membrane. [87] For selective permeability, the incorporation of natural channels into the membrane or of chemically/genetically-modified ones to respond to the presence of external stimuli is required to facilitate access of substrates to the encapsulated enzymes. [88,89] Different methods for permeabilizing polymer membranes are discussed below.…”

Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development

“…Hydrophilic polymers such as PEG, , poly­(2-methyl-2-oxazoline) (PMOXA), poly­(acrylic acid) (PAA), and poly­( N -isopropylacrylamide) (PNIPAAm) have been employed as shell-forming blocks in ABCPs (Figure and Table ). The shell-forming block plays a crucial role in providing steric stability to polymersomes during their storage and in vivo circulation.…”

“…The separation of the core-forming hydrophobic blocks from the surrounding aqueous media supported by strong cohesive forces is crucial for the formation of stable polymeric systems and incorporation of payloads. In other words, stability is tightly tied to physicochemical properties of the hydrophobic block such as stiffness, crystallinity, cross-linking in the polymer segments, and interactions governing drug incorporation including π–π stacking and electrostatic or hydrogen bonding. − Hydrophobic blocks include poly­(butadiene) (PBD), ,, poly­(propylene sulfide) (PPS), − poly­(styrene) (PSt), poly­(dimethylsiloxane) (PDMS), and poly­[2-(diisopropylamino)-ethyl methacrylate] (PDPA) (Figure and Table ). Despite their lack of biodegradability, incorporating PEG through conjugation renders the block copolymers biocompatible .…”