Celastrol-Based Nanomedicine Hydrogels Eliminate Posterior Capsule Opacification

Abstract

Aim: To formulate an injectable thermosensitive micelle–hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-β1. Celastrol prevents epithelial–mesenchymal transition in lens epithelial cells induced by TGF-β1 through the TGF-β1/Smad2/3/TEAD1 signaling pathway. In vivo efficiency evaluations showed that CMG demonstrated an excellent inhibitory effect on PCO in rabbits and had no obvious tissue toxicity. Conclusion: Injectable CMG may represent a promising ophthalmic platform for preventing PCO. This versatile injectable micelle–hydrogel hybrid represents a clinically relevant platform to achieve localized therapy and controlled release of drugs in other disease therapies.

Keywords::

• celastrol
• epithelial–mesenchymal transition
• hydrogel
• nanomedicine
• posterior capsule opacification

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2022-0191

Financial & competing interests disclosure

This research was supported by the National Natural Science Foundation of China (52173143 and 82101090), the Medical Science and Technology Project of Henan Province (LHGJ20210062) and the Basic Science Key Project of Henan Eye Hospital (20JCZD002, 20JCQN001 and 22JCQN001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (52173143 and 82101090), the Medical Science and Technology Project of Henan Province (LHGJ20210062) and the Basic Science Key Project of Henan Eye Hospital (20JCZD002, 20JCQN001 and 22JCQN001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.