Probing and Tuning the Permeability of Polymersomes

Abstract

Polymersomes are a class of synthetic vesicles composed of a polymer membrane surrounding an aqueous inner cavity. In addition to their overall size, the thickness and composition of polymersome membranes determine the range of potential applications in which they can be employed. While synthetic polymer chemists have made great strides in controlling polymersome membrane parameters, measurement of their permeability to various analytes including gases, ions, organic molecules, and macromolecules remains a significant challenge. In this Outlook, we compare the general methods that have been developed to quantify polymersome membrane permeability, focusing in particular on their capability to accurately measure analyte flux. In addition, we briefly highlight strategies to control membrane permeability. Based on these learnings, we propose a set of criteria for designing future methods of quantifying membrane permeability such that the passage of a variety of molecules into and out of their lumens can be better understood.

Tuneable Time Delay in the Burst Release from Oxidation‐Sensitive Polymersomes Made by PISA

“…Apart from that, the high activity observed for the encapsulated GOx indicates an inherent size‐selective permeability of the PNAT membrane towards small hydrophilic molecules, such as glucose or H 2 O 2 , while slightly larger molecules, such as calcein, and the macromolecule GOx, were retained in the vesicular lumen. As PNAT features a high glass transition temperature, this intrinsic permeability of the membrane likely originates from increased hydration of the PNAT domain, [33] similar to previous observations for PHPMA‐based systems [2b, 5a, 34] . Subsequent to these permeability studies, we assessed whether the H 2 O 2 generation of the encapsulated GOx is sufficient to induce the oxidation of the thioether groups and finally destabilize the vesicular membrane.…”

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

“…Amphiphilic block copolymers have been widely employed for the formulation of polymer vesicles (i.e., polymersomes) [ 347 ] and recent efforts have been focused on investigating and modulating the membrane permeability of such vesicles toward the development of nanoreactors. [ 348 ] These systems typically encapsulate a bioactive enzyme in their aqueous compartment and are semipermeable to the enzyme substrates and reaction products. The membrane permeability can be tuned by varying the polymer chain length or the hydrophilic‐to‐lipophilic balance, which affect the membrane thickness.…”

“…The membrane permeability can be tuned by varying the polymer chain length or the hydrophilic‐to‐lipophilic balance, which affect the membrane thickness. [ 348 ] Semipermeable polymersomes are currently under investigation as nanoreactors for therapeutic applications. Poly(2‐hydroxypropyl methacrylate) (PHPMA)‐based polymersomes whose membrane is semipermeable to l‐asparagine and encapsulating l‐asparaginase have been shown to convert l‐asparagine into aspartic acid and ammonia; these nanoreactors have been proposed for the treatment of acute lymphoblastic leukemia.…”

Supramolecular chemistry in lipid bilayer membranes

“…6 More recently, amphiphilic block copolymers have been used to form vesicles (polymersomes), which benefit from improved stability against dilution and enhanced chemical diversity. 7 A detailed discussion of the various experimental techniques available is beyond the scope of this perspective, and we direct the reader to a number of review articles on the subject. 3,5 Molecular recognition and sensing at a bilayer interface using membrane-bound receptors Confinement of supramolecular receptors within a lipid bilayer membrane leads to an increase in effective concentration by many orders of magnitude, because the receptors are confined to the volume of the membrane.…”