Advances in Ophthalmic Drug Delivery

Morrison, Peter W. J.; Khutoryanskiy, Vitaliy V.

doi:10.4155/tde.14.75

Cited by 167 publications

(127 citation statements)

References 101 publications

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“…6 The ocular drug bioavailability of topically applied formulations is typically below 5%. 7,8 The low bioavailability is due to multiple factors, including fast clearing of the drug from the surface of the eye, drug solubility, and protective mechanisms and barriers of the cornea. 2,9 The apical layer of the corneal epithelium forms tight junctions and presents the main ratelimiting step to the majority of topically applied lipophilic drugs.…”

mentioning

confidence: 99%

New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies

Kaluzhny

Kinuthia

Truong

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of the current work was to develop a physiologically relevant, in vitro human three-dimensional (3D) corneal epithelial tissue model for use in ophthalmic drug development.METHODS. Normal human corneal epithelial cells were cultured at the air-liquid interface to produce the 3D corneal tissue model. Corneal barrier was determined by measuring transepithelial electrical resistance (TEER). Quantitative PCR arrays were utilized to investigate expression of 84 phase I/II metabolizing enzymes and 84 drug transporter genes. Permeability was evaluated using model compounds with a wide range of hydrophobicity, molecular weight, and excipients. Finally, different formulations of latanoprost and bimatoprost were administered and drug absorption and tissue viability and integrity were investigated.RESULTS. Histologic assessment and TEER of the corneal tissue model revealed tissue structure, thickness, and barrier formation (1000 6 146 XÁcm 2 ) comparable to native human corneal epithelium. The 3D corneal tissue expressed tight junctions, mucins, and key corneal epithelial detoxification enzymes. Drug-metabolizing enzyme and transporter gene expression in 3D corneal tissue and excised human corneal epithelium were highly correlated (r 2 ¼ 0.87). Coefficients of permeation for model drugs in the tissue model and excised rabbit corneas also showed a high correlation (r 2 ¼ 0.94). As expected, latanoprost and bimatoprost free acids had much lower permeability (Papp ¼ 1.2 3 10 À6 and 1.9 3 10 À6 ) than the corresponding prodrugs (Papp ¼ 2.5 3 10 À5 and 5.6 3 10 À5 ), respectively. The presence of 0.02% benzalkonium chloride in ophthalmic formulations significantly affected tissue barrier and viability.CONCLUSIONS. The newly developed 3D corneal tissue model appears to be very useful for evaluation of corneal drug permeability and safety during ophthalmic drug development.

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mentioning

confidence: 99%

New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies

Kaluzhny

Kinuthia

Truong

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Several commercially available CLs were FDA approved to serve this purpose: Pure Vision (balafilcon A, Bausch+Lomb), Acuvue 2 (etafilcon A, Vistakon Inc.), Acuvue Oasys (senofilcon A, Vistakon Inc.), and Air Optix Night & Day (lotrafilcon A, Alcon). [13][14][15]19 …”

Section: Retention Strategiesmentioning

confidence: 99%

“…There are already available in the market injectable intraocular implants to treat several chronic eye diseases ensuring a drug sustained release for 2.5-3 years: Iluvien TM (Alimera Sciences Inc.) for diabetic macular edema, RetisertÒ (Baush &Lomb) and OzurdexÒ (Allergan) for chronic non-infectious posterior uveitis and Durasert TM (Pfizer Inc.) for glaucoma. 14,[17][18] Several drug retention strategies have been pursued to minimize the need for repeated treatments, especially in chronic diseases. They comprise viscosity-enhancing polymers, "in situ" gels undergoing phase transition from liquid to gel under physiological conditions, mucoadhesives and mucus-covered mucosal epithelial membranes, and nanoparticles drug-delivery systems as submicron structures in which drugs can be attached or encapsulated.…”

mentioning

confidence: 99%

Contact lenses as drug controlled release systems: a narrative review

Filipe¹,

Henriques²,

Reis³

et al. 2016

Revista Brasileira De Oftalmologia

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Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of RESUMOA forma mais frequente de aplicação terapêutica em oftalmologia consiste na instilação de gotas oculares, mas dadas as limitações anatómicas e fisiológicas do olho, é necessária dosagem frequente com possível repercussão na adesão do paciente à terapêutica. Nas últimas décadas, as lentes de contacto (CLs) têm surgido como um potencial sistema de libertação controlada de fármacos na superfície ocular (DCRS) para correção do erro refrativo. Está em curso uma extensa investigação para entender a melhor forma de modificar as CLs, de modo a aumentar o tempo de residência e a biodisponibilidade do medicamento na superfície ocular dentro de níveis terapêuticos. Ao corrigirem a ametropia, estes dispositivos poderão simultaneamente desempenhar um papel na gestão de perturbações oftalmológicas, tais como a síndrome do olho seco, glaucoma, alergia ocular e infecção corneana, que podem comprometer o porte seguro e confortável das CLs. Nesta revisão narrativa, os autores explicam como as estruturas da superfície ocular determinam a difusão de fármacos no olho e sintetizam as estratégias para aumentar a permanência e biodisponibilidade dos mesmos. Em seguida, apresentam os resultados e as aplicações clínicas das CLs embebidas em fármacos, como DCRS, através da incorporação de barreiras de difusão, de monómeros funcionais, da liberação controlada por iões, da impressão molecular, de nanopartículas e pelo processo camada sobre camada. Os autores concluem avaliando o impacto destes novos sistemas de entrega de agentes farmacológicos ao melhorar o seu transporte no tecido alvo, reduzindo a sua absorção sistémica e os seus efeitos colaterais indesejáveis, e discutem perspectivas futuras.

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“…The efforts made by many researchers in the last decades to optimize drug delivery through soft contact lenses (SCLs) have been described in several recent reviews [1][2][3]. In the case of cataracts which are, nowadays, one of the most frequent eye diseases, other devices have been investigated to prevent postoperative infectious complications after surgery, namely, therapeutic intraocular lenses (IOLs) [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…(1) incorporation of chemical agents that can interact reversibly with the drug [7]; (2) the use of nanocarriers, such as micelles, liposomes or nanoparticles [8,9]; (3) introduction of diffusion barriers to the drugs, such as Vitamin E aggregates [10,11].…”

Section: Introductionmentioning

confidence: 99%