Abstract
Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA–lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.
Highlights
Liposomes are a well-accepted drug delivery system and still the most common nanomedicines in clinical trials [1]
The DSPE–hyaluronic acid (HA) conjugate was analyzed with 1H-nuclear magnetic resonance spectroscopy (NMR) and Fourier-transform infrared spectroscopy (FT-IR) spectroscopy (Figure S1, Supplementary Materials)
A novel HA–lipid conjugate was successfully synthesized for the preparation of light-activated indocyanine green liposomes
Summary
Liposomes are a well-accepted drug delivery system and still the most common nanomedicines in clinical trials [1]. Most liposomal carriers are coated with polyethylene glycol (PEG) to prolong their residence times in blood circulation [2,3], but there are still problems related to reduced uptake into the target cells [3,4], immunogenicity [5,6], and undesired protein interactions [7]. Alternatives for PEG were proposed, including polyvinylpyrrolidone (PVP) [8], polycarbonates [9], pullulan [10], polyoxazolines [11], and hyaluronic acid (HA) or hyaluronan [12]. The HA coating combines steric stabilization (“stealth”) and active targeting functions. HA improves liposomal stability in freeze-drying due to its high water-binding capacity [15]
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