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.

Brain targeted delivery of rapamycin using transferrin decorated nanostructured lipid carriers

“…According to our previous research, Precirol ATO5 and Capryol PGMC with the highest rapamycin solubility capacity were selected respectively as solid and liquid lipid ingredients of NLCs (11). For the preparation of C-NLCs the solvent diffusion-ultrasonication method was used.…”

“…According to our previous study, Precirol ATO5 and Capryol PGMC were selected respectively as solid and liquid lipid ingredients of NLCs. 11 Here stearylamine plays as a cationic lipid and creates a positive charge for physical adsorption of transferrin on the surface of NLCs through electrostatic interaction.…”

“…According to our previously reported study, Precirol ATO5 and Capryol PGMC were selected as solid and liquid lipids respectively. 11 Cationic-NLCs (C-NLCs), containing SA as cationic lipid, were prepared by emulsification solvent diffusion-evaporation method the following ultrasonication. Briefly, Precirol ATO5, SA, Capryol PGMC, and rapamycin were dissolved in ethanol at 50ºC and dispersed in the aqueous surfactant solution at 50ºC using a magnetic stirrer at 1000 rpm.…”

Inhibition of Neovascularization and Inflammation in a Mouse Model of Corneal Alkali Burns Using Cationic Liposomal Tacrolimus

“…Except for small corneal scrapes, the damaged cornea is unable to return to its original transparency. After a corneal injury, when the corneal stromal cells transform into activated fibroblasts, the reflectivity of the corneal stromal cells is increased, thereby enhancing the turbidity of the cornea ( Zahir-Jouzdani et al, 2019 ). In addition to causing severe tissue damage, corneal alkali burns can also cause the production of many growth factors and inflammatory cytokines, which promote corneal opacity after injury.…”

Appraising the Competency of Lipid Nano-Platforms as Non-invasive Paradigms for the Treatment of Ocular Inflammations: A review

“…Rapa loading into NLC resolved the drug limitations such as hydrophobicity and instability in the presence of heat, light, and extreme pH conditions. The uptake of the developed Rapa-NLC was enhanced into fibroblasts, proving significant antifibrotic and anti-angiogenetic corneal activity when injured, and hence conserving corneal transparency [59].…”