Polymersomes
are attractive nanocarriers for hydrophilic and lipophilic
drugs; they are more stable than liposomes, tunable, and relatively
easy to prepare. The copolymer composition and molar mass are critical
features that determine the physicochemical properties of the polymersomes
including the rate of drug release. We used the triblock-copolymer,
poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA–PDMS–PMOXA),
to form amphipathic polymersomes capable of loading proteins and small
hydrophobic agents. The selected agents were unstable neurotrophins
(nerve growth factor and brain-derived neurotrophic factor), a large
protein CD109, and the fluorescent drug curcumin. We prepared, characterized,
and tested polymersomes loaded with selected agents in 2D and 3D biological
models. Curcumin-loaded and rhodamine-bound PMOXA–PDMS–PMOXA
polymersomes were used to visualize them inside cells. N-Methyl-d-aspartate receptor (NMDAR) agonists and antagonists
were also covalently attached to the surface of polymersomes for targeting
neurons. Labeled and unlabeled polymersomes with or without loaded
agents were characterized using dynamic light scattering (DLS), UV–vis
fluorescence spectroscopy, and asymmetrical flow field-flow fractionation
(AF4). Polymersomes were imaged and tested for biological
activity in human and murine fibroblasts, murine macrophages, primary
murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes
were rapidly internalized and there was a clear intracellular co-localization
of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled
polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored
protein, promoted cell migration in the model of wound healing. Nerve
growth factor-loaded polymersomes effectively enhanced neurite outgrowth
in dissociated and explanted dorsal root ganglia. Brain-derived neurotrophic
factor increased dendritic spine density in serum-deprived hippocampal
slice cultures. NMDAR agonist- and antagonist-functionalized polymersomes
targeted selectively neurons over glial cells in mixed cultures. Collectively,
the study reveals the successful incorporation into polymersomes of
biologically active trophic factors and small hydrophilic agents that
retain their biological activity in vitro, as demonstrated in selected
central and peripheral tissue models.