Current Ocular Drug Delivery Challenges for N-acetylcarnosine: Novel Patented Routes and Modes of Delivery, Design for Enhancement of Therapeutic Activity and Drug Delivery Relationships

Abstract

This review article explores the functional activity and development aspects of N-acetylcarnosine for the visual system as revealed by the use of a variety of biophysical, physiological and therapeutic ophthalmic methods. It is designed for pharmacists and more advanced ophthalmology, optometry and pharmacology researchers who wish to gain a basic understanding of the biological effects of N-acetylcarnosine for vision and to share in the excitement of the latest developments in this field. Topics under the consideration include: ophthalmic drug delivery of N-acetylcarnosine eye drops and challenging endeavors facing the pharmaceutical scientist; clinical and functional types of activity of the developed and patented N-acetylcarnosine lubricant eye drops designed as 1% N-acetylcarnosine prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a drug delivery system; management of age-related serious or disabling eye diseases in humans with N-acetylcarnosine eye drop therapeutic platform (age-related cataracts, ocular inflammation, age-related macular degeneration , macular dystrophies, ocular manifestations of diabetes , hypertonic retinopathy, primary open angle glaucoma, vitreous lesions) ; development and molecular mechanisms of ocular therapeutic activities of carnosine derivatives in the visual system. Through this article we can perceive some helpful recent patents according to the title of the issue. The biologically significant applications of carnosine mimetics including those in ophthalmology were patented by Dr. Babizhayev and the alliance Groups (WO 2004/028536 A1; WO 94/19325; WO 95/12581; WO 2004/064866 A1).

Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

“…Based on our own studies, we have suggested that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine and carcinine [9,10]. Cumulatively, in this article, we propose that patented specific oral formulations of nonhydrolyzed carnosine and carcinine provide a powerful tool for targeted inhibition of cumulative oxidative stress and inflammation associated with telomere shortening in age-related diseases and during smoking behavior ( Figure 8, Table 1) [9,10,15,132,135,143,171]. This product concept implements the potential role of the Oral product for safe therapeutic manipulation with molecular chaperones, telomeres, and telomerase biology; N-acetylcarnosine lubricant eye drops and oral product comprising carnosine, D-pantethine, or regulated/inducible molecular chaperone protein function (such as α-crystallin chaperone activity in the lens) offer potential novel therapies for reversal of (ripe) cataracts, retinal degeneration, and ocular complications of diabetes.…”

“…Carnosine, released ophthalmically from N-acetylcarnosine prodrug lubricant eye drops, at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to oxidative stress in the lack of efficient antioxidant lens protection (B). The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement compared, in contrast to the control group that showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings [14,15].…”

“…It can oppose glycation [140,141] and it can chelate divalent metal ions [142]. The important studies have produced clinical and experimental evidence of beneficial effects of N-acetylcarnosine in treating cataracts of the eyes; these and other ophthalmological benefits have been proven [14,15,[143][144][145][146][147][148][149][150][151]. Carcinine (β-alanyl histamine) is an imidazole dipeptide first discovered in the crustacean Carcinus maenas (reviewed in refs.…”

“…Potential therapeutic applications of oral forms of nonhydrolyzed carnosine and their specific mechanisms to manage telomere attrition and vascular aging might help elderly patients to withstand the problems of sight-threatening eye diseases related to oxidative stress and accelerated biological aging in linked with earlier onset of diseases. Left, pronounced opacities in the lens layers prior cataract treatment; right, an appearance of the rose reflex visible through the lens, which became significantly more transparent after 5 months of combined treatment of ripe cataract with the 1% N-acetylcarnosine lubricant eye drop combined with the oral supplementation of Can-C Plus ™ [15,171].…”

“…Biological activities of the nonhydrolyzed carnosine in the oral formulation are based on its antioxidant and antiglycating (transglycating) action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing sight-threatening eye disorders having oxidative stress in their pathogenesis, neurodegeneration, and accumulation of senile features. The findings suggest that synergism is required between carnosine or other imidazole-containing compounds and reduced glutathione in tissues and cells for efficacious protection from protein carbonylation as a biomarker for the ability of the nontoxic compounds to reduce oxidative stress [9,10,15,132,135,143,171]. Potential therapeutic applications of oral forms of nonhydrolyzed carnosine and their specific mechanisms to manage telomere attrition and vascular aging might help elderly patients and smokers to withstand the pathogenetic problems of age-related disorders, metabolic and smoking-related diseases, accompanying with cumulative oxidative stress, accumulation of advanced glycation products, and accelerated biological aging linked with earlier onset of diseases [9,10,132,135,143,171].…”