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Nanostructured lipid carriers containing rapamycin for prevention of corneal fibroblasts proliferation and haze propagation after burn injuries: In vitro and in vivo
Author(s) -
ZahirJouzdani Forouhe,
Khonsari Fatemeh,
Soleimani Masoud,
Mahbod Mirgholamreza,
Arefian Ehsan,
Heydari Mostafa,
Shahhosseini Saeed,
Dinarvand Rassoul,
Atyabi Fatemeh
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27243
Subject(s) - cornea , in vivo , myofibroblast , burn injury , in vitro , medicine , pharmacology , fibrosis , cancer research , chemistry , pathology , biology , ophthalmology , surgery , biochemistry , microbiology and biotechnology
Chemical burns are a major cause of corneal haze and blindness. Corticosteroids are commonly used after corneal burns to attenuate the severity of the inflammation‐related fibrosis. While research efforts have been aimed toward application of novel therapeutics. In the current study, a novel drug delivery system based nanostructured lipid carriers (NLCs) were designed to treat corneal alkaline burn injury. Rapamycin, a potent inhibitor of mammalian target of rapamycin pathway, was loaded in NLCs (rapa‐NLCs), and the NLCs were characterized. Cell viability assay, cellular uptake of NLCs, and in vitro evaluation of the fibrotic/angiogenic genes suppression by rapa‐NLCs were carried out on human isolated corneal fibroblasts. Immunohistochemistry (IHC) assays were also performed after treatment of murine model of corneal alkaline burn with rapa‐NLCs. According to the results, rapamycin was efficiently loaded in NLCs. NLCs could enhance coumarin‐6 fibroblast uptake by 1.5 times. Rapa‐NLCs efficiently downregulated platelet‐derived growth factor and transforming growth factor beta genes in vitro. Furthermore, proliferation of fibroblasts, a major cause of corneal haze after injury, reduced. IHC staining of treated cornea with alpha‐smooth muscle actin and CD34 + antibodies showed efficient prevention of myofibroblasts differentiation and angiogenesis, respectively. In conclusion, ocular delivery of rapamycin using NLCs after corneal injury may be considered as a promising antifibrotic/angiogenic treatment approach to preserve patient eyesight.