Hyaluronic acid coated albumin nanoparticles for targeted peptide delivery in the treatment of retinal ischaemia
Abstract
Recent studies have shown that Connexin43 mimetic peptide (Cx43 MP) can prevent secondary damage following retinal ischaemic and inflammatory disorders by blocking uncontrolled Cx43 hemichannel opening. However, limitations in peptide stability and the presence of various intraocular barriers limit efficient retinal delivery in the clinical setting. The present study aimed to achieve targeted and sustained peptide delivery to the retina by encapsulating Cx43 MP into hyaluronic acid (HA) coated albumin nanoparticles (NPs). Intraocular biodistribution, particle retention, retinal targeting, and therapeutic efficacy of intravitreally injected NPs encapsulating Cx43 MP were evaluated in a rat model of retinal ischaemia-reperfusion injury. NPs rapidly diffused through the vitreous and specifically targeted CD44-expressing retinal cells. NPs remained at the target site for extended periods enabling sustained peptide release and thus prolonged therapeutic action. Compared to free Cx43 MP, Cx43 MP loaded NPs enabled enhanced therapeutic efficacy preventing thinning of retinal layers and disruption of retinal blood vessels. Immunohistochemical results confirm that Cx43 MP loaded NPs efficiently reduced Cx43 expression, thereby suppressing ongoing inflammation and preventing the loss of retinal ganglion cells. Overall, HA coated NPs could have great potential as a peptide delivery platform in the treatment of chronic retinal degenerative and inflammatory disorders.
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Strategies such as PEGylation, charge modification, and coating with hyaluronate or chloroquine have been shown to improve retinal transduction in animal models when administered intravitreally.
“Strategies such as PEGylation [271], charge modification [272], and coating with hyaluronate or chloroquine [273,274] have been shown to improve retinal transduction in animal models when administered intravitreally.”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [273]
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- Authors
- Huang, D., Chen, Y.-S., Green, C. R., & Rupenthal, I. D.
- Affiliations
- University of Auckland (NZ)
- Corresponding author
- Rupenthal, Ilva D.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 168
- Pages
- 10-23
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2790638053
- Cited by
- 85
- References
- 58
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 11 · 2021: 21 · 2020: 6 · 2019: 12 · 2018: 1
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Council of New Zealand (14/018)
- Buchanan Charitable Foundation
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- retinal drug delivery, CD44 targeting, intravitreal injection, sustained peptide release, retinal inflammation, retinal degeneration
- MeSH terms
- Albumins, Animals, Cell Line, Drug Carriers, Hyaluronic Acid, Ischemia, Male, Peptides, Retinal Diseases, Rats, Wistar, Connexin 43, Rats, Nanoparticles
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