Bioavailability of vitamin B<sub>12</sub> using a small‐volume nebulizer ophthalmic drug delivery system

Kahn, Mon-Te

doi:10.1111/j.1442-9071.2005.01030.x

Cited by 12 publications

(10 citation statements)

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“…Perhaps the water-soluble nature of vitamin B12 is an obstacle to penetration into the ocular compartment, and the use of repeated subconjunctival injection, 55 small-volume nebulizer, 56 and more recently, periocular injection of in situ hydrogels 57 or subconjunctival biodegradable microfilms 58 may be a more efficient means to deliver the cofactor in these patients. Clearly, research on potential therapeutics would be enhanced significantly if a viable animal model of cblC deficiency could be generated and studied.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

et al. 2016

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Ocular manifestations of cobalamin C deficiency include a developmental as well as a degenerative phenotype and lack strict correlation to metabolic status, but may be mitigated by prenatal or early treatment. Purpose To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism caused by mutations in the MMACHC gene. Design Retrospective, observational case series. Participants Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health Clinical Center between August 2004 and September 2012. Patient ages ranged from 2 to 27 years at last ophthalmic visit, and follow-up ranged from 0 to 83 months (median, 36 months; range, 13–83 months) over a total of 69 visits. Methods Best-corrected Snellen visual acuity, slit-lamp biomicroscopy, dilated fundus examination, wide-field photography, fundus autofluorescence imaging, sedated electroretinography, spectral-domain optical coherence tomography, and metabolite assessment. Main Outcome Measures Visual acuity and presence and degree of retinal degeneration and optic nerve pallor. Results Nystagmus (64%), strabismus (52%), macular degeneration (72%), optic nerve pallor (68%), and vascular changes (64%) were present. c.271dupA (p.R91KfsX14) homozygous patients (n = 14) showed early and extensive macular degeneration. Electroretinography showed that scotopic and photopic responses were reduced and delayed, but were preserved remarkably in some patients despite severe degeneration. Optical coherence tomography images through the central macular lesion of a patient with severe retinal degeneration showed extreme thinning, some preservation of retinal lamination, and nearly complete loss of the outer nuclear layer. Despite hyperhomocysteinemia, no patients exhibited lens dislocation. Conclusions This longitudinal study reports ocular outcomes in the largest group of patients with cblC deficiency systematically examined at a single center over an extended period. Differences in progression and severity of macular degeneration, optic nerve pallor, and vascular attenuation between homozygous c.271dupA (p.R91KfsX14) patients and compound heterozygotes were noted. The pace and chronicity of ophthalmic manifestations lacked strict correlation to metabolic status as measured during visits. Prenatal or early treatment, or both, may have mitigated ocular disease, leading to better functional acuity, but patients still progressed to severe macular degeneration. The effects of prenatal or early treatment, or both, in siblings, the manifestation of severe disease in infancy, the presence of comorbid developmental abnormalities (e.g., microcephaly, cardiac noncompaction), and the possible laminar structural defect noted in many patients are findings showing that cblC deficiency displays a developmental as well as a degenerative ocular phenotype.

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Section: Discussionmentioning

confidence: 99%

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

et al. 2016

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“…Camphor and menthol also forms a hydrophobic eutectic mixture. Camphor and menthol are powerful penetration enhancers (8)(9)(10)(11)(12)(13)(14). Camphor and menthol cause leaching of the lipids present in the skin and thus cause subsequent pore formation (25).…”

Section: Resultsmentioning

confidence: 99%

“…The probable reason for this difference could be presence of camphor and menthol in batch B16. It is reported that camphor and menthol works as penetration enhancer (8). Camphor and menthol causes leaching of the lipids present in the skin and thus causes pore formation (24).…”

Section: Factorial Designmentioning

confidence: 99%

“…A 3 2 full factorial design was employed for optimization. The formulation contained eutectic mixture of menthol and camphor (dermal penetration enhancers) that readily partition into the stratum corneum (8)(9)(10)(11)(12)(13)(14). Eutectic mixture of camphor and menthol also acted as a solvent for film-forming polymers, imparted cooling effect to the skin and possessed antifungal activity (15,16).…”

Section: Introductionmentioning

confidence: 99%

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Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers

Gohel

Nagori

2009

AAPS PharmSciTech

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Abstract. The present investigation was undertaken to fabricate modified transport fluconazole transdermal spray using ethyl cellulose and Eudragit® RS100 as film-forming polymers. Eudragit® RS100 (X 1 ) and ethyl cellulose (X 2 ) were selected as independent variables in 3 2 full factorial design, whereas drug transport in first hour (Y 1 ) and the time required for 50% drug transport (Y 2 ) were selected as dependent variables. Eutectic blend of camphor and menthol was used as permeation enhancer cum solvent for film-forming polymers. The pH, viscosity, volume of solution delivered upon each actuation, spray angle, ex-in vivo physical evaluation and in vitro drug transport of the formulated products were evaluated. The optimized batch B16 containing 5.25% w/w ethyl cellulose and 10.6% w/w Eudragit® RS100 was formulated by overlapping the contour plots of Y 1 and Y 2 . The pH, viscosity, volume of solution sprayed upon each actuation and spray angle of the batch B16 was 6.3, 52.9 cPs, 0.24 ml and 82.6°r espectively. The film of optimized batch was flexible and dermal-adhesive. The responses Y 1 and Y 2 of batch B16 were 7.91 μg/ml and 347 min respectively. The kinetics of drug transport was best explained by the Korsmeyer and Peppas model. The eutectic mixture consisting of equal parts of camphor and menthol showed improved drug permeation through shed snake skin. Short-term stability study demonstrated insignificant changes in performance characteristics.

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“…An eye mister, if tolerated by veterinary patients, could have a profound effect on improving compliance, especially in large animals or possibly zoo animal patients with ocular disease. In one study, an ultrasonic nebulizer was used to create a mist of vitamin B12 that was delivered to the ocular surface in humans and compared with a control group that received a topical eye drop of vitamin B12 49 . Twelve hours later, aqueous humor was collected and analyzed for B12 concentrations.…”

Section: Ocular Drug Deliverymentioning

confidence: 99%

Advancements in ocular drug delivery

Weiner

Gilger

2010

Veterinary Ophthalmology

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This review covers both noninvasive and invasive ophthalmic drug delivery systems that can have application to therapy of veterinary ophthalmic diseases. Noninvasive approaches include gel technologies, permeation enhancement via pro-drug development, solubilization agents and nanoparticle technologies, iontophoresis, microneedles, drug-eluting contact lenses and eye misters, and microdroplets. More invasive systems include both eroding implants and noneroding technologies that encompass diffusion based systems, active pumps, intraocular lenses, suprachoroidal drug delivery, and episcleral reservoirs. In addition to addressing the physiologic challenges of achieving the necessary duration of delivery, tissue targeting and patient compliance, the commercial development factors of biocompatibility, sterilization, manufacturability and long-term stability will be discussed.

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Bioavailability of vitamin B₁₂ using a small‐volume nebulizer ophthalmic drug delivery system

Abstract: The small-volume nebulizer system might provide another method of ophthalmic drug delivery.

Cited by 12 publications

References 12 publications

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers

Advancements in ocular drug delivery

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Bioavailability of vitamin B12 using a small‐volume nebulizer ophthalmic drug delivery system

Abstract: The small-volume nebulizer system might provide another method of ophthalmic drug delivery.

Cited by 12 publications

References 12 publications

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency

Fabrication of Modified Transport Fluconazole Transdermal Spray Containing Ethyl Cellulose and Eudragit® RS100 as Film Formers

Advancements in ocular drug delivery

Contact Info

Product

Resources

About

Bioavailability of vitamin B₁₂ using a small‐volume nebulizer ophthalmic drug delivery system