Macromolecule-based
therapeutic agents, particularly proteins,
antigens, monoclonal antibodies, transcription factors, nucleic acids,
and gene editing enzymes, have the potential to offer cures for previously
untreatable diseases. However, they present an enormous delivery challenge
due to poor absorption and rapid metabolism in the body. Polymersomes
have tremendous potential in delivering these agents to their desired
intracellular location due to increased circulation times, decreased
macromolecule degradation, and decreased immune responses. In this
Review, we highlight the key factors in design, development, and improved
performance of these vesicles for macromolecular delivery. The recent
progress made toward preclinical application of these vesicles for
protein and gene delivery is also covered.
Self-assembled polymersomes encapsulate, protect, and deliver hydrophobic and hydrophilic drugs. Though spherical polymersomes are effective, early studies suggest that non-spherical structures may enhance specificity of delivery and uptake due to similarity to endogenous uptake targets. Here we describe a method to obtain persistent non-spherical shapes, prolates, via osmotic pressure and the effect of prolates on uptake behavior. Polyethylene glycol-b-poly(lactic acid) polymersomes change in diameter from 175 ± 5nm to 200 ± 5nm and increase in polydispersity from 0.06 ± 0.02 to 0.122 ± 0.01 nm after addition of 50 mM salt. Transmission and scanning electron microscopy confirm changes from spheres to prolates. Prolate-like polymersomes maintain their shape in 50 mM NaCl for seven days. Nile Red and bovine serum albumin(BSA)-.
In drug delivery, enzyme-responsive drug carriers are becoming increasingly relevant because of the growing association of disease pathology with enzyme overexpression. Polymersomes are of interest to such applications because of their tunable properties. While polymersomes open up a wide range of chemical and physical properties to explore, they also present a challenge in developing generalized rules for the synthesis of novel systems. Motivated by this issue, in this perspective, we summarize the existing knowledge on enzyme-responsive polymersomes and outline the main design choices. Then, we propose heuristics to guide the design of novel systems. Finally, we discuss the potential of an integrated approach using computer simulations and experimental studies to streamline this design process and close the existing knowledge gaps.
This paper highlights the potential
benefits of using self-assembled
polymeric nanoparticles of various shapes to enhance drug uptake.
First, we highlight the growth and development of the polymersome,
using a liposome as a blueprint for amphiphilic codelivery. Then,
we focus on the advantages of nanoparticle elongation, drawing from
the field of solid nanoparticles, as opposed to self-assembled vesicles
which have not yet been extensively explored in shape-modulated drug
delivery applications. Notably, regardless of the material used in
the solid nanoparticle systems, more elongated shapes lead to greater
cellular uptake, decreased interaction with the reticuloendothelial
system macrophages, and increased circulation times. Finally, we highlight
the methods currently being developed to modulate polymersome shape,
thus providing a drug delivery system with the benefits derived from
amphiphilicity and elongated structures. Current methods employed
to modulate polymersome shape involve osmotic pressure gradients,
solvent switching, and the use of cross-linking agents. Although these
methods are successful in modulating polymersome shapes and the benefits
of elongated nanoparticles in therapeutic targeting are clear, these
methods have not yet been explored for applications in drug delivery.
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