Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells

Abstract

Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H2O2-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes.

Antiseptics and the Ocular Surface: In Vitro Antimicrobial Activity and Effects on Conjunctival and Corneal Epithelial Cells of a New Liposomal Ocular Spray Containing Biosecur® Citrus Extract

“…On the basis of our findings, we hypothesize that the liposomal formulation of the ocular spray tested is responsible for the reduction of the toxicity of the antiseptic Biosecur on conjunctival and corneal epithelial cells in vitro. Our hypothesis is also supported by previous studies which reported that liposomal formulations are able to reduce the toxicity of different drugs for ocular tissues [ 18 , 19 ] and conjunctival and corneal cells in vitro [ 20 ]. Liposomes have in fact some advantages over most ophthalmic delivery systems: they are biodegradable, biocompatible, relatively nontoxic, and they can provide an intimate contact with the corneal surface [ 21 ].…”

Tacrolimus Loaded Cationic Liposomes for Dry Eye Treatment

“…In this study, cationic FK506 liposomes were proven to prolong ocular retention time and increase FK506 amount in the cornea; at the same time, this treatment alleviated the signs of dry eye and reduced the expression of inflammatory factors in vitro and in vivo. Landucci et al (2021) developed a thymoquinone-loaded liposome and found that it could reduce the toxicity at high dose in HCEC-2 cells. Huang et al (2017) constructed the liposome encapsulating montmorillonite and betaxolol hydrochloride to treat glaucoma and found that liposomal formulation could effectively reduce cytotoxicity of betaxolol hydrochloride.…”

Prospects and hot spots for mammalian target of rapamycin in the field of neuroscience from 2002 to 2021

“…Although this is the first bibliometric study of mTOR in neuroscience, there are some limitations that have been reported in other bibliometric study papers ( Chen et al, 2020 ; Landucci et al, 2021 ; Ma et al, 2021 ). The deadline for publication of this study is 31 December 2021, but the WoSCC will be updated constantly.…”