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A single molecule carrier for ocular posterior segment diseases.

Xiao-Ling Zhang¹, Yu-Xin Yue², Yang Yang¹

¹Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300392, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society

|November 3, 2024

Summary

This study introduces a novel single molecule nanomedicine using sulfonated azocalix[4]arene (SAC4A) for targeted ocular drug delivery. The nanomedicine significantly improves drug transport to the posterior eye segment, enhancing treatment for diseases like wet age-related macular degeneration.

Keywords:

Drug delivery Eye drop Host-guest recognition Ocular posterior segment disease Single molecule carrier

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Area of Science:

Nanomedicine
Ocular Drug Delivery
Host-Guest Chemistry

Background:

Ocular posterior segment diseases present a challenge for non-invasive eye drop treatments due to complex biological barriers.
Efficient drug delivery to the posterior eye segment is crucial for treating conditions like wet age-related macular degeneration (wAMD).

Purpose of the Study:

To develop a single molecule nanomedicine for enhanced ocular drug delivery to the posterior segment.
To utilize host-guest chemistry for targeted delivery and controlled release of therapeutic agents.
To demonstrate the efficacy of this nanomedicine approach in a preclinical model of wAMD.

Main Methods:

Sulfonated azocalix[4]arene (SAC4A) was employed as a single molecule carrier.
Complexation of SAC4A with sunitinib (SUN) to form SUN@SAC4A eye drops.
Evaluation of drug transport to the retinal-choroid tissue and anti-angiogenesis effects in a wAMD model.

Main Results:

SAC4A demonstrated favorable characteristics including small size, negative charge, hydrophilicity, and hypoxia-triggered release.
The SUN@SAC4A formulation significantly increased sunitinib delivery to the posterior segment (2.47 times higher than SUN alone at 30 min).
Enhanced anti-choroidal neoangiogenesis effect was observed, highlighting therapeutic potential for wAMD.

Conclusions:

Single molecule nanomedicine based on SAC4A offers a promising strategy for overcoming ocular barriers and improving drug delivery to the posterior eye segment.
This approach holds potential for treating various ocular posterior segment diseases, including wAMD.
The host-guest chemistry-based nanomedicine paradigm facilitates efficient drug transport and therapeutic outcomes.