Journal
PHARMACEUTICS
Volume 12, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics12080763
Keywords
hyaluronic acid; liposome; drug release; light activation; stability; mobility; biocorona
Categories
Funding
- Academy of Finland [311122, 317336]
- Business Finland [4208/31/2015]
- EU Horizon 2020 Marie Sklodowska-Curie Innovative Training Networks NANOMED project [676137]
- Orion Research Foundation [9-8214-9]
- Phospholipid Research Center
- Emil Aaltonen Foundation
- Instrumentarium Science Foundation
- Mary and GeorgC. Ehrnrooth Foundation
- Evald and Hilda Nissi Foundation
- Inkeri and Mauri Vanska Foundation
- Paulo Foundation
- Paivikki and Sakari Sohlberg Foundation
- University of Helsinki
- Academy of Finland (AKA) [317336, 317336] Funding Source: Academy of Finland (AKA)
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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 (similar to 5 nm hard, similar to 10 nm soft coronas) than in vitreous (similar to 2 nm hard, similar to 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.
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