2. Academic Validation
  3. Targeted dexamethasone nano-prodrug for corneal neovascularization management

Targeted dexamethasone nano-prodrug for corneal neovascularization management

  • Biomed J. 2023 Mar 31;S2319-4170(23)00029-X. doi: 10.1016/j.bj.2023.03.005.
Qichuan Yin 1,  Haijie Han 1,  Kexin Shi 1,  Jiayue Zhou 1,  Sifan Zheng 2,  Ke Yao 3,  Xingchao Shentu 4
Affiliations

Affiliations

  • 1 Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, 310009, China.
  • 2 GKT School of Medical Education, King's College London, London, SE1 1UL, England.
  • 3 Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, 310009, China. Electronic address: [email protected].
  • 4 Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, 310009, China. Electronic address: [email protected].
PMID: 37004870 DOI: 10.1016/j.bj.2023.03.005
Abstract

Background: To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated APRPG peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA).

Methods: Characterization of DPA nano-prodrug were measured with transmission electron microscopy (TEM) and dynamic LIGHT scattering (DLS) analyses. Cytotoxicity and effects on cell migration and tube formation of DPA were evaluated in vitro. A murine CNV model was established by cornea alkali burn. The injured corneas were given eye drops of DPA (0.2 mM), Dex solution (0.2 mM), Dexp (2 mM), or normal saline three times a day. After two weeks, eyes were obtained for the analysis of histopathology, immunostaining, and mRNA expression.

Results: DPA with an average diameter of 30 nm, presented little cytotoxicity and had good ocular biocompatibility. More importantly, DPA showed specific targeting to vascular endothelial cells with efficient inhibition on cell migration and tube formation. In a mouse CNV model, clinical, histological, and immunohistochemical examination results revealed DPA had a much stronger angiogenesis suppression than Dex, resembling a clinical drug with an order of magnitude higher concentration. This was ascribed to the significant downregulations in the expression of pro-angiogenic and pro-inflammatory factors in the corneas. In vivo imaging results also demonstrated that APRPG could prolong ocular retention time.

Conclusions: This study suggests that DPA nano-prodrug occupies advantages of specific targeting ability and improved bioavailability over conventional therapy and holds great potential for safe and efficient CNV therapy.

Keywords

angiogenic vessel-homing peptide; corneal neovascularization; dexamethasone; nano-prodrug; targeted drug delivery.

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