Design and Applications of Polymersomes for Oral Drug Administration

Abstract

Polymersomes are nanostructures consisting of a hollow aqueous compartment enclosed by a coating of amphiphilic block copolymers. Owing to the entangled nature of their membrane, polymersomes exhibit higher mechanical stability than some other extensively studied nanostructures such as liposomes. This also enables the properties of the polymersome membrane to be more easily tuned to meet practical needs, making polymersomes promising carriers for drug delivery. Since the turn of the last century, the use of polymersomes has been exploited in diverse areas, ranging from protein therapy to medical imaging. Yet, discussions exploring the opportunities and challenges of the development of polymersomes for oral drug administration have been scant. This review addresses this gap by offering a snapshot of the current advances in the design, fabrication, and use of polymersomes as oral drug carriers. It is hoped that this review will not only highlight the practical potential of polymersomes for oral drug administration but will also shed light on the challenges determining the wider clinical potential of polymersomes in the forthcoming decades.

Keywords: amphiphilicity; block copolymers; colloidal behavior; controlled release; drug delivery; oral administration; polymersomes.

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Schematic diagram illustrating the different morphologies of self-assembled structures formed by amphiphilic block copolymers.

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Schematic diagram depicting the formation of drug-loaded polymersomes, which can be achieved by (A) mixing drug molecules with the amphiphilic block copolymer during the self-assembly process or (B) loading drug molecules into preformed polymersomes after self-assembly.

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(A) Fabrication of the Y-shaped microfluidic device and the subsequent generation of polymersomes. (B) Transmission electron micrographs of the polymersomes (i) before and (ii) after drug loading. Scale bar = 200 nm. Reproduced with permission from ref . Copyright 2024 Elsevier BV.

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Overview of the major roles played by polymersomes as carriers for oral drug delivery.

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SEM images of (A) polymersomes and (B) micelles. TEM images of doxorubicin-loaded (C) polymersomes and (D) micelles. Reproduced with permission from ref . Copyright 2015 Springer Nature.

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(A) Schematic diagram depicting the flow self-assembly setup. (B–D) TEM micrographs of self-assembled structures obtained from PAA-b-PS. (E) Phase diagram depicting changes in the self-assembled structures under different combinations of pH and tetrahydrofuran content. In the figure, M, P, and S denote micelles, polymersomes, and solid particles, respectively. Reproduced with permission from ref . Copyright 2024 John Wiley & Sons, Inc.

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(A) Schematic diagram showing the process of node formation and node elongation on the surface of polymersomes. The process is achieved by adding a diblock copolymer, namely PT, which contains complementary thymine side chains and is synthesized via aqueous reversible addition–fragmentation chain-transfer polymerization-induced self-assembly, onto the polymersome membrane. (B) Dry-state and cryo-TEM images depicting the formation and lengthening of nodes on the surface of the polymersomes. Reproduced with permission from ref . Copyright 2024 Royal Society of Chemistry.

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(A) Chemical structure of PAA, which imparts negative charges to the surface of micelles. (B) TEM micrograph and (C) intensity-averaged dynamic light scattering data of the negatively charged micelles. (D) Chemical structure of quaternized poly­(4-vinylpyridine), which imparts positive charges to the surface of polymersomes. (E) TEM micrograph and (F) intensity-averaged dynamic light scattering data of the positively charged polymersomes. (G) Schematic diagram depicting the formation of polymersomes with micellar patches. Reproduced with permission from ref . Copyright 2024 Elsevier BV.