Nanostructured lipid carriers containing rapamycin for prevention of corneal fibroblasts proliferation and haze propagation after burn injuries: In vitro and in vivo.

Abstract

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.

• Authors: Forouhe Zahir-Jouzdani, Fatemeh Khonsari, Masoud Soleimani, Mirgholamreza Mahbod, Ehsan Arefian, Mostafa Heydari, Saeed Shahhosseini, Rassoul Dinarvand, Fatemeh Atyabi
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 234 Issue 4 Pg. 4702-4712 (04 2019) ISSN: 1097-4652 [Electronic] United States
• PMID: 30191977 (Publication Type: Journal Article)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Drug Carriers
• Lipids
• Sodium Hydroxide
• Sirolimus

Topics

• Administration, Ophthalmic
• Animals
• Burns, Chemical (drug therapy, etiology, metabolism, pathology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cornea (drug effects, metabolism, pathology)
• Corneal Injuries (chemically induced, drug therapy, metabolism, pathology)
• Corneal Neovascularization (chemically induced, metabolism, pathology, prevention & control)
• Corneal Opacity (chemically induced, drug therapy, metabolism, pathology)
• Disease Models, Animal
• Drug Carriers
• Drug Compounding
• Eye Burns (chemically induced, drug therapy, metabolism, pathology)
• Fibroblasts (drug effects, metabolism)
• Fibrosis
• Humans
• Lipids (chemistry)
• Male
• Mice, Inbred BALB C
• Nanomedicine
• Nanoparticles
• Sirolimus (administration & dosage, chemistry)
• Sodium Hydroxide
• Wound Healing (drug effects)