Novel everolimus-loaded nanocarriers for topical treatment of murine experimental autoimmune uveoretinitis (EAU)

In the present study, tissue distribution and the therapeutic effect of topically applied cyclosporine A (CsA)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly(lactic acid) (mPEGhexPLA) nanocarriers (ApidSOL) on experimental autoimmune uveitis (EAU) were investigated. The CsA-loaded mPEGhexPLA nanocarrier was tolerated well locally and showed no signs of immediate toxicity after repeated topical application in mice with EAU. Upon unilateral CsA treatment, CsA accumulated predominantly in the corneal and sclera-choroidal tissue of the treated eye and in lymph nodes (LN). This regimen reduced EAU severity in treated eyes compared to PBS-treated controls. This improvement was accompanied by reduced T-cell count, T-cell proliferation, and IL-2 secretion of cells from ipsilateral LN. In conclusion, topical treatment with CsA-loaded mPEGhexPLA nanocarriers significantly improves the outcome of EAU.

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“…The emulsion was injected subcutaneously at the base of the tail. 36,37 Mice were sacrificed on day 21 postimmunization (p. i.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis

Kasper

Gabriel²,

Möller

et al. 2018

Mol. Pharmaceutics

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“…For example, Dactolisib can be delivered into a target site using pegylated PLGA NPs with high cell up-take potential, and this makes them an ideal candidate in drug delivery [271]. Moreover, Kasper et al synthesized a modern nanocarrier for topical delivery of everolimus [268]. They prepared a nanostructure based on methoxy-poly (ethylene-glycol)-hexyl substituted poly (lactic acid) (mPEGhexPLA) and then loaded everolimus into the nanocarriers.…”

Section: Nanostructures For Autophagy Modulator Delivery Systemsmentioning

confidence: 99%

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems

et al. 2019

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Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.

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“…Everolimus, 4 O - O -(2-hydroxyethyl)-rapamycin, a hydroxy derivative of rapamycin, is a lipophilic 31-membered ring lactone compound isolated from Streptomyces hygroscopicus (Schuler et al., 1997; Kasper et al., 2018). In recent years, it has been found to specifically inhibit helper T lymphocytes, and has anti-immuno-rejection and anti-tumor activities (Herrera-Gómez et al., 2017; Huijts et al., 2017; Li et al., 2018; Wu et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, it has been found to specifically inhibit helper T lymphocytes, and has anti-immuno-rejection and anti-tumor activities (Herrera-Gómez et al., 2017; Huijts et al., 2017; Li et al., 2018; Wu et al., 2019). Studies have shown that it can be used in eyes such as autoimmune uveoretinitis, noninfectious uveitis, corneal neovascularization and immune-mediated rejection after corneal transplantation (Li et al., 2008; Çakmak et al., 2016; Blair et al., 2017; Kasper et al., 2018). Clinically, immune rejection diseases caused by organ transplantation including corneal transplantation are mostly treated by systemic administration such as oral administration, which is easy to cause systemic immunosuppressive effects and cause serious adverse reactions (Cotovio et al., 2012; Renner et al., 2012; Jebali et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Preparation and study of two kinds of ophthalmic nano-preparations of everolimus

Yin

Zhang

et al. 2019

Drug Delivery

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Objective: To prepare everolimus nanoformulations and increase their solubility to suit their application in the eye. Methods: The everolimus micelles was prepared by thin film dispersion method using Tween-80 (P80) and polyoxyethylene stearate (P40S) as carriers. In addition, the everolimus nanosuspension was prepared by injection method using poloxamer 407 (P407), hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as stabilizers. It was characterized in terms of particle size, PDI and encapsulation efficiency or drug loading. The in vitro release and in vitro rabbit scleral permeability characteristics were investigated, and the pharmacokinetics of anterior chamber drug in rabbit eyes were studied. Results: The average particle size of the micelles was (8.74 ± 0.21) nm, the encapsulation efficiency and drug loading were (90.12 ± 1.18)% and (2.14 ± 0.028)%, while the average particle size of the nanosuspension was (156.47 ± 1.10) nm, and the drug loading was (16.51 ± 0.21)%, respectively. Both in vitro release and rabbit scleral permeation models were consistent with the Higuchi equation. The pharmacokinetic experiments of aqueous humor showed that area under the curve of everolimus nanosuspension was about 3 times higher than that of micelles. Micelles could be achieved in the eye and maintained for a long time. Conclusion: The preparation of everolimus micelles or nanosuspension for eye are suitable for ocular administration and expected to be new dosage form for corneal transplantation immunological rejection or other ocular disease. ARTICLE HISTORY

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Novel everolimus-loaded nanocarriers for topical treatment of murine experimental autoimmune uveoretinitis (EAU)

Cited by 16 publications

References 48 publications

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems

Preparation and study of two kinds of ophthalmic nano-preparations of everolimus

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