Dataset Information

Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

ABSTRACT: Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits. In a choroidal melanoma-bearing mouse model, eyedrops containing FCS/anti-PDL1 could induce stronger antitumor immune responses than those triggered by intravenous injection of anti-PDL1. Moreover, in choroidal neovascularization-bearing mouse and rabbit models, FCS/anti-VEGFA eyedrops effectively inhibited vascular proliferation, achieving comparable therapeutic responses to those observed with intravitreal injection of anti-VEGFA. Our work presents an effective delivery carrier to treat fundus diseases using eyedrop of therapeutic proteins, which may enable at-home treatment of many eye diseases with great patient compliance.

SUBMITTER: Shen J

PROVIDER: S-EPMC9882978 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

Shen Jingjing J Gao Huiqin H Chen Linfu L Jiang Yutong Y Li Shu S Chao Yu Y Liu Nanhui N Wang Yufei Y Wei Ting T Liu Yan Y Li Jipeng J Chen Muchao M Zhu Jiafei J Liang Juan J Zhou Xiaoyu X Zhang Xiaofeng X Gu Ping P Chen Qian Q Liu Zhuang Z

Science advances 20230127 4

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments ...[more]

PMID: 36706184

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Project description:Objective Osteoarthritis (OA) is a painful degenerative disease of the whole joint structure, including articular cartilage, synovial fluid, and subchondral bone. Hyaluronic acid (HA), an anionic non-sulfated glycosaminoglycan, is commonly used for intra-articular (IA) treatment in OA, while bisphosphonates (BPs) are anti-resorptive drugs that act on the bone. Here, a novel conjugate with a covalent and hydrolysable linker between HA and alendronate (ALD) was designed as an attractive therapeutic strategy for IA drug delivery. Design The HA-ALD derivative was synthesized and tested in comparison with a simple mixture of HA and ALD for in vitro ALD release, rheological properties, cytotoxicity towards osteoblasts and chondrocytes and in an in vitro efficacy assay of OA inflammatory model on bovine cartilage explants. Results The structure of HA-ALD was elucidated exhibiting no depolymerization and efficient drug incorporation. The controlled ALD release in vitro was slower compared to the simple mixture of HA and ALD; moreover, the derivative showed calcium-tuned rheological properties. The absence of cytotoxicity towards osteoblasts and chondrocytes was shown for up to 7 days, and the viability of chondrocytes was confirmed by fluorescence microscopy. Finally, a reduction in collagen release and MMP-13 expression was measured in the OA inflammatory model. Conclusion This new HA-ALD derivative opens the door to a new approach for OA treatment, as it combines viscosupplementation and biological effects of HA with the pharmacological activity of BPs. Prolonged ALD release increased rheological properties and beneficial effect against cartilage degradation make it a promising IA therapy for OA. Graphical abstract Image 1 Highlights • Development of an IA treatment to target OA pathogenesis rather than symptoms.• A novel hyaluronan-alendronate conjugate was synthesized with a reversible linker.• The drug delivery system confirmed slow alendronate release.• The efficacy was demonstrated in an osteoarthritis inflammatory model.• New intra-articular treatment: viscosupplementation and pharmacological activity.

Dataset Information

Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

Publications

Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

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