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Combination Nanomedicine Strategy for Preventing High-Risk Corneal Transplantation Rejection
Tuo Meng1, Jinhua Zheng1,2, Crystal S Shin3
1Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia 23298, United States.
Abstract:
High-risk (HR) corneal transplantation presents a formidable challenge, with over 50% of grafts experiencing rejection despite intensive postoperative care involving frequent topical eyedrop administration up to every 2 h, gradually tapering over 6-12 months, and ongoing maintenance dosing. While clinical evidence underscores the potential benefits of inhibiting postoperative angiogenesis, effective antiangiogenesis therapy remains elusive in this context. Here, we engineered controlled-release nanomedicine formulations comprising immunosuppressants (nanoparticles) and antiangiogenesis drugs (nanowafer) and demonstrated that these formulations can prevent HR corneal transplantation rejection for at least 6 months in a clinically relevant rat model. Unlike untreated corneal grafts, which universally faced rejection within 2 weeks postsurgery, a single subconjunctival injection of the long-acting immunosuppressant nanoparticle alone effectively averted graft rejection for 6 months, achieving a graft survival rate of ∼70%. Notably, the combination of an immunosuppressant nanoparticle and an anti-VEGF nanowafer yielded significantly better efficacy with a graft survival rate of >85%. The significantly enhanced efficacy demonstrated that a combination nanomedicine strategy incorporating immunosuppressants and antiangiogenesis drugs can greatly enhance the ocular drug delivery and benefit the outcome of HR corneal transplantation with increased survival rate, ensuring patient compliance and mitigating dosing frequency and toxicity concerns.
Insights
New nanomedicine formulations prevent high-risk corneal transplant rejection. A single injection of immunosuppressant nanoparticles or a combination with anti-VEGF nanowafer significantly improved graft survival in a rat model.
Area of Science:
- Ophthalmology
- Nanomedicine
- Immunology
Background:
- High-risk corneal transplantation has a high graft rejection rate (>50%) despite intensive immunosuppression.
- Effective anti-angiogenesis therapy for preventing graft rejection remains a clinical challenge.
Purpose of the Study:
- To engineer and evaluate controlled-release nanomedicine formulations for preventing high-risk corneal transplant rejection.
- To assess the efficacy of single-agent immunosuppressant nanoparticles and combination therapy with anti-angiogenesis drugs.
Main Methods:
- Development of controlled-release nanomedicine formulations containing immunosuppressants (nanoparticles) and anti-angiogenesis drugs (nanowafer).
- Evaluation of nanomedicine efficacy in a clinically relevant rat model of high-risk corneal transplantation.
- Assessment of graft survival rates following subconjunctival injection of nanomedicine formulations.
Main Results:
- A single subconjunctival injection of immunosuppressant nanoparticles alone prevented graft rejection for 6 months, achieving ~70% graft survival.
- Combination therapy with immunosuppressant nanoparticles and anti-VEGF nanowafer significantly enhanced efficacy, with >85% graft survival.
- Untreated corneal grafts were universally rejected within 2 weeks post-surgery.
Conclusions:
- Combination nanomedicine strategy incorporating immunosuppressants and anti-angiogenesis drugs significantly improves outcomes in high-risk corneal transplantation.
- This approach enhances ocular drug delivery, increases graft survival rates, and addresses patient compliance and toxicity concerns.
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