Preparation and in vitro/in vivo evaluations of novel ocular micelle formulations of hesperetin with glycyrrhizin as a nanocarrier

Zhang, Fan; Chen, Huabo; Lan, Jie; Song, Kaichao; Wu, Xianggen

doi:10.1016/j.exer.2020.108313

Cited by 21 publications

(5 citation statements)

References 48 publications

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“…However, unexpectedly, we found that neutral pH GLY optimally reduced plate count over acidic treatment. Our data parallels other studies in a rabbit model of S. aureus infection, where protection was shown after topical GLY-based nanodrug formulations containing thymol (pH 7.4) (Song et al, 2020), or hesperetin (pH 7.0) (Zhang et al, 2021). Similarly, in a transgenic hepatitis B mouse model, treatment with GLY (pH not specified) significantly decreased the intrahepatic recruitment of neutrophils and other inflammatory cells after cytotoxic T lymphocyte injection (Sitia et al, 2007).…”

Section: Discussionsupporting

confidence: 88%

“…Neither was pH considered in other animal models, in which GLY is protective, including in lung (Ni et al, 2011) and cerebral ischemic (Gong et al, 2014) injuries, colitis (Liu et al, 2011), and sepsis (Wang et al, 2013). In contrast, in other studies, ophthalmic solutions containing GLY as nanocarriers at neutral pH were used to treat Staphylococcus aureus infection in rabbits (Song et al, 2020;Zhang et al, 2021) and corneal wounds in diabetic mice (Hou et al, 2021a). In this regard, pilot clinical studies have investigated the efficacy of GLY in ophthalmic solutions (all at neutral pH) to treat blepharitis (Mencucci et al, 2013) and dry eye disease (Burillon et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Ocular Effects of Glycyrrhizin at Acidic and Neutral pH

Somayajulu

McClellan

Bessert

et al. 2022

Front. Cell. Infect. Microbiol.

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PurposeTo test the effects of acidic vs. neutral pH glycyrrhizin (GLY) on the unwounded and wounded normal mouse cornea and after infection with Pseudomonas aeruginosa isolates KEI 1025 and multidrug-resistant MDR9.MethodsAcidic or neutral GLY vs. phosphate-buffered saline (PBS) was topically applied to normal or wounded corneas of C57BL/6 mice. In unwounded corneas, goblet cells and corneal nerves were stained and quantitated. After wounding, corneas were fluorescein stained and photographed using a slit lamp. Mice also were infected with KEI 1025 or MDR9 and the protective effects of GLY pH evaluated comparatively.ResultsIn the unwounded cornea, application of acidic or neutral GLY vs. PBS reduced the number of bulbar conjunctival goblet cells but did not alter corneal nerve density. Similar application of GLY to scarified corneas delayed wound closure. After KEI 1025 infection, none of the GLY vs. PBS-treated corneas perforated; GLY treatment also decreased plate count (neutral pH more effective) and reduced MPO and several cytokines. Similarly, for MDR9, GLY at either pH was protective and also enhanced the effects of moxifloxacin to which MDR9 is resistant.ConclusionAcidic or neutral pH GLY decreased goblet cell number but had no effect on nerve density. After corneal wounding, GLY at either pH (1) delayed wound closure and, (2) after infection, decreased keratitis when used alone or in combination with moxifloxacin. Neutral pH did not alter the therapeutic effect of GLY and would be preferred if used clinically.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Ocular Effects of Glycyrrhizin at Acidic and Neutral pH

Somayajulu

McClellan

Bessert

et al. 2022

Front. Cell. Infect. Microbiol.

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“…DG-Hes ophthalmic solution also significantly reduced the symptoms of ocular infection in a rabbit model of bacterial keratitis compared with Hes suspension. These results suggest that DG-Hes eye drops may be useful as a new ophthalmic agent for the treatment of ocular diseases, particularly bacterial eye diseases [176].…”

Section: Micelle Eye Drop Delivery Systemsmentioning

confidence: 84%

Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye

Wang

2022

Pharmaceutics

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Eye drops are the most common and convenient route of topical administration and the first choice of treatment for many ocular diseases. However, the ocular bioavailability of traditional eye drops (i.e., solutions, suspensions, and ointments) is very low because of ophthalmic physiology and barriers, which greatly limits their therapeutic effect. Over the past few decades, many novel eye drop delivery systems, such as prodrugs, cyclodextrins, in situ gels, and nanoparticles, have been developed to improve ophthalmic bioavailability. These novel eye drop delivery systems have good biocompatibility, adhesion, and propermeation properties and have shown superior performance and efficacy over traditional eye drops. Therefore, the purpose of this review was to systematically present the research progress on novel eye drop delivery systems and provide a reference for the development of dosage form, clinical application, and commercial transformation of eye drops.

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“…69 Nanomicelles are emerging as a promising platform for the delivery of poorly water-soluble drugs to the eye due to their increased bioavailability, enhanced corneal permeation, and increased solubility and stability of drugs. [70][71][72][73] Zhao et al reported a nanomicelle drug delivery system made of a copolymer EPC (nEPC), comprising PEG, polypropylene glycol (PPG), and polycaprolactone (PCL) for the topical instillation of aflibercept to the posterior segment of the eye. nEPCs were made by concentrating EPC above the critical micelle concentration but below the concentration required for sol-gel transition.…”

Section: Nanomicellesmentioning

confidence: 99%