Design and Evaluation of Voriconazole Eye Drops for the Treatment of Fungal Keratitis

Malhotra, Sakshi; Khare, Anubha; Grover, Kanchan; Singh, Inderbir; Pawar, Pravin

doi:10.1155/2014/490595

Cited by 14 publications

(17 citation statements)

References 13 publications

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“…61 The permeability of the widely used topical antibiotic OFL (small, not charged molecule) was slightly lower than expected (Papp ¼ 9.2 6 2.1 3 10 À6 ) from studies with excised rabbit corneas (Papp ¼ 1.5 6 0.1 3 10 À5 ). 63,64 Since in vivo and excised rabbit corneas are considered to be gold standards for ocular drug delivery analysis, correlation coefficients were determined for 3D corneal model versus published data (Table 3). 10,52,61À66 The apparent permeability coefficients (P app ) obtained from the model drugs in the in vitro 3D corneal tissues were compared to P app obtained in excised rabbit corneas.…”

Section: Permeation Of Model Compoundsmentioning

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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Section: Permeation Of Model Compoundsmentioning

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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“…[8,9] Additionally, there is evidence that changes to other delivery factors have minimal effects on ocular penetration such as increased drop size (due to the limited conjunctival volume) [8] or increased viscosity (which may increase residence time but decrease corneal permeation). [10,11] Conjunctiva and nasal absorption of drug In addition to the primary physiological barriers discussed above, another major barrier that acts to decrease drug concentration at the site of the absorptive membrane is the systemic absorption of drug through the dense and compact vascularisation of blood and lymphatic capillaries in the conjunctiva and nasal cavity. [12] Depending on the therapeutic drug, this mechanism can increase systemic adverse effects ranging from hypotension and bradycardia in timolol to palpitations and headaches in adrenaline eye drops, especially in paediatric and elderly cohorts.…”

Section: Primary Physiological Barriersmentioning

confidence: 99%

Delivery of therapeutics for deep-seated ocular conditions – status quo

Nguyen

Eng

Ngo

et al. 2018

Journal of Pharmacy and Pharmacology

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Objectives There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Key findings Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Summary Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance.

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“…The plates were left for 30 min and incubated at 25°C ± 1°C for 24 hours. After that zone of inhibitions were measured [24].…”

Section: In Vitro Antifungal Activitymentioning

confidence: 99%

Water Soluble Chitosan Mediated Voriconazole Microemulsion as Sustained Carrier for Ophthalmic Application: In vitro/Ex vivo/In vivo Evaluations

Bhosale¹,

Bhandwalkar²,

Duduskar³

et al. 2016

PHARMSCI

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Background: Voriconazole (VCZ) is a lipophilic candidate, effective against fungal infections like ocular keratitis and endopthalmitis. Objective: The purpose to develop, optimize and characterize voriconazole microemulsion as sustained medication for ophthalmic application. Methods: The pseudo-ternary phase diagrams were developed using oleic acid, isopropyl myristate and isopropyl palmitate (oil phases), tween 80 (surfactant), propylene glycol (co-surfactant), distilled water (aqueous phase) and modified chitosan (Mod.CH) as mucoadhesive polymer. The optimum composition of oil, Smix and water was selected on the basis of phase diagrams and as mucoadhesive polymer Mod.CH was used in the formulations. All the formulations were evaluated for thermodynamic stability/dispersibility, physicochemical parameters (droplet size, polydispersity index, zeta potential, drug content, viscosity, pH and conductivity), in vitro, ex vivo and in vivo studies. Results: All formulations showed droplet size below 250 nm, positive zeta potential and polydispersity index below 0.5. The in vitro drug release study performed on selected formulations showed maximum sustained release than marketed formulation. The in vitro transcorneal permeation experiment of formulations suggests that optimized formulations showed better permeation. The selected formulation of voriconazole microemulsion was able to produce maximum antifungal activity against Candida albicans when compared to marketed formulation. In vivo study performed on rabbit eyes, found more drug concentration in aqueous humor of optimized formulation; the AUC0→t of IPMVM-11 was approximately 6.84-fold higher than VOZOLE and efficiently enhanced the corneal bioavailability. Conclusion: The modified chitosan based on voriconazole loaded microemulsion was promising novel carrier for sustained action in ophthalmic medication.

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Design and Evaluation of Voriconazole Eye Drops for the Treatment of Fungal Keratitis

Cited by 14 publications

References 13 publications

New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies

New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies

Delivery of therapeutics for deep-seated ocular conditions – status quo

Water Soluble Chitosan Mediated Voriconazole Microemulsion as Sustained Carrier for Ophthalmic Application: In vitro/Ex vivo/In vivo Evaluations

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