Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection
Abstract
Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.
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The dual-drug delivery system might be a hopeful formulation for suppressing corneal graft failure.
“Overall, this dual-drug delivery system might be a hopeful formulation for suppressing corneal graft failure [147].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [147]
Topical instillation of Lev@RAPA micelle-loaded NapFFKK hydrogel resulted in excellent ocular tolerance and extended precorneal retention exceeding 60 min, significantly improving ocular bioavailability of both Lev and RAPA.
“Topical instillation of this formulation resulted in excellent ocular tolerance and extended precorneal retention exceeding 60 min, which significantly improved the ocular bioavailability of both Lev and RAPA.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [147]
Lev@RAPA micelle-loaded NapFFKK hydrogel provided sustained in vitro drug release without undermining inherent pharmacological activities.
“The Lev@RAPA micelle loaded NapFFKK hydrogel provided sustained in vitro drug release without undermining their inherent pharmacological activities.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [147]
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References 64 · Cited by 14
- Authors
- Xu, X., Wu, Y., Gu, R., Zhang, Z., Liu, X., Hu, Y., Li, X., Lin, D., & Bao, Z.
- Affiliations
- Wenzhou Medical University (CN)
- Corresponding author
- Li, Xingyi
- Lin, Deqing
- Bao, Zhishu
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 201
- Pages
- 114351
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W4399418368
- Cited by
- 14
- References
- 64
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Zhejiang Province Natural Science Foundation (LGF22H180023)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- corneal graft rejection, rapamycin, levofloxacin, ocular bioavailability, topical ocular drug delivery, sustained drug release, precorneal retention, immunosuppression, corneal graft failure
- MeSH terms
- Animals, Biological Availability, Cornea, Drug Carriers, Graft Rejection, Immunosuppressive Agents, Male, Micelles, Rabbits, Corneal Transplantation, Drug Delivery Systems, Hydrogels, Sirolimus, Nanoparticles, Levofloxacin, Drug Liberation
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