title: Ocular drug metabolism of the bioactivating antioxidant N-acetylcarnosine for vision in ophthalmic prodrug and codrug design and delivery.
abstract: The basic idea in this study relates to the interesting research problem to employ with the knowledgeable pharmacy staff N-acetylcarnosine (NAC) in the developed suitable compounded prodrug ophthalmic preparations, which are currently used for the treatment of cataract and have antioxidant effect, in order to provide the molecular support to one of the most popular beliefs of the growing market for the treatment of senile cataract in patients and animals with efficacious NAC drug formulations worldwide patented by the author. This work presents the progress in ocular NAC prodrug and codrug design and delivery in light of revealed ocular metabolic activities. There is a considerable interest in the ophthalmic codrug design including NAC prodrug based on the strategies to improve ophthalmic drug delivery of the active peptide principal L-carnosine through the sustained intraocular metabolic activation of a dipeptide while making it resistant to enzymatic hydrolysis. Novel approaches to ocular NAC drug delivery, developed by Innovative Vision Products, Inc. (IVP), aim at enhancing the drug bioavailability by ensuring a prolonged retention of the medication in the eye, and/or by facilitating transcorneal penetration. IVP team studied the effects of lubricant eye drops designed as 1% NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based and corneal absorption promoters in a drug delivery system. The predicted responses of the corneal and conjunctival penetrations to the synergistic promoters are useful in controlling the extent and pathway of the ocular and systemic absorptions of instilled NAC prodrug in designed ophthalmic formulations thereof. Utility of peptidase enzyme inhibitors in the codrug formulation to modulate the transport and metabolism of NAC prodrug appears to be a promising strategy for enhancing dipeptide drug transport across the cornea. The developed and officially CE mark registered by IVP NAC prodrug and codrug lubricating eye drop systems (including principal regulatory registered eye drops design and lubricating eye drops marketed under numerous brand labels), increase the intraocular uptake of the active principle L-carnosine from its ophthalmic carrier NAC in the aqueous humor and the permeability of a drug into the eye, and so enhance the ocular bioavailability, bioactivating universal antioxidant, and anti-cataract efficacy (in human and in canine eyes) of the developed NAC eye drops.
authors.affiliation: Innovative Vision Products, Silverside Road, Suite, County of New Castle, Delaware, USA. markbabizhayev@ mail.ru
authors.forename: Mark A
authors.initials: MA
authors.lastname: Babizhayev
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics*; D002336:Carnosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D002386:Cataract / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism; D015195:Drug Design; D005123:Eye / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism; D015227:Lipid Peroxidation; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011355:Prodrugs / Q000493:pharmacokinetics*; D011817:Rabbits
chemical_list: D000975:Antioxidants; D008081:Liposomes; D011355:Prodrugs; C033681:N-acetylcarnosine; D002336:Carnosine