Novel micelle carriers for cyclosporin A topical ocular delivery: In vivo cornea penetration, ocular distribution and efficacy studies

Tommaso, Claudia Di; Bourges, Jean‐Louis; Valamanesh, F.; Trubitsyn, Gregory; Torriglia, Alicia; Jeanny, Jean-Claude; Behar‐Cohen, Francine; Gurny, Robert; Möller, Michael

doi:10.1016/j.ejpb.2012.02.014

Cited by 118 publications

(88 citation statements)

References 36 publications

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“…33 The particle size of a polymer nanoparticle is a key factor related to its ability to pass through biological membranes and has a significant effect on the rate of its ocular penetration in ophthalmic applications. Additionally, larger sized particles may lead to a scratching feeling based on foreign body sensation.…”

mentioning

confidence: 99%

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Li¹,

Li²,

Zhou³

et al. 2015

IJN

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Purpose The cornea is a main barrier to drug penetration after topical application. The aim of this study was to evaluate the abilities of micelles generated from a positively charged triblock copolymer to penetrate the cornea after topical application. Methods The triblock copolymer poly(ethylene glycol)-poly(ε-caprolactone)- g -polyethyleneimine was synthesized, and the physicochemical properties of the self-assembled polymeric micelles were investigated, including hydrodynamic size, zeta potential, morphology, drug-loading content, drug-loading efficiency, and in vitro drug release. Using fluorescein diacetate as a model drug, the penetration capabilities of the polymeric micelles were monitored in vivo using a two-photon scanning fluorescence microscopy on murine corneas after topical application. Results The polymer was successfully synthesized and confirmed using nuclear magnetic resonance and Fourier transform infrared. The polymeric micelles had an average particle size of 28 nm, a zeta potential of approximately +12 mV, and a spherical morphology. The drug-loading efficiency and drug-loading content were 75.37% and 3.47%, respectively, which indicates that the polymeric micelles possess a high drug-loading capacity. The polymeric micelles also exhibited controlled-release behavior in vitro. Compared to the control, the positively charged polymeric micelles significantly penetrated through the cornea. Conclusion Positively charged micelles generated from a triblock copolymer are a promising vehicle for the topical delivery of hydrophobic agents in ocular applications.

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confidence: 99%

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Li¹,

Li²,

Zhou³

et al. 2015

IJN

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“…However, in cases where the surgery is high risk, the success rate is drastically reduced to 50%. 23 Minimization of the inflammatory response reduces corneal NV after corneal transplantation and increases graft survival.…”

Section: Diseases Related To Corneal Nvmentioning

confidence: 99%

Nanotechnology in Corneal Neovascularization Therapy—A Review

Gonzalez

Loza

Han

et al. 2013

Journal of Ocular Pharmacology and Therapeutics

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Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels.1 The term ''nanotechnology'' was first coined in 1974. 2 Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. 3 The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.

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“…1,5 Because of its hydrophobicity with poor water solubility (0.012 mg/mL at 25°C), CsA must be solubilized in nonaqueous media that include surfactants, such as Cremophor EL, as in the case of Sandimmune ® (Novartis International AG, Basel, Switzerland). [6][7][8] As an immunosuppressant, CsA at a low concentration has been shown to be useful for patients with inflammatory ocular surface disorders, including dryeye syndrome. Dry-eye syndrome is a disorder of the tear film, occurring as a result of tear deficiency or excessive evaporation.…”

Section: Introductionmentioning

confidence: 99%

“…7 Therefore, a micelle formulation is effective in delivering CsA into corneal layers and ocular tissues, allowing successful local CsA action. However, thus far there have been few studies on CsA-micelle formulations used to treat dry-eye syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, almost none of the delivery systems has been fully satisfactory. 1,7 Ikervis ® (1 mg/mL CsA; Santen Pharmaceutical Co Ltd, Osaka, Japan), which has recently been introduced to EU markets, is a CsA formulation that can help alleviate dry-eye syndrome. However, its milky white emulsion poses some challenges, especially patient compliance.…”

Section: Introductionmentioning

confidence: 99%

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Cyclosporine A micellar delivery system for dry eyes

Kang¹,

Ho²,

Cho³

et al. 2016

IJN

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Background The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. Materials and methods CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. Results MS-CsA had a smaller particle size (average diameter 14–18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups ( P <0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83±8.38, a significantly higher result than the 65.17±11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. Conclusion The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes.

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Novel micelle carriers for cyclosporin A topical ocular delivery: In vivo cornea penetration, ocular distribution and efficacy studies

Cited by 118 publications

References 36 publications

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Nanotechnology in Corneal Neovascularization Therapy—A Review

Cyclosporine A micellar delivery system for dry eyes

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