Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform

Drug Test Anal. 2012 Jun;4(6):468-85. doi: 10.1002/dta.265. Epub 2011 Mar 18.


A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of the study document that the therapeutic benefit in clinical trials is associated with the bioactivation universal antioxidant and transglycating properties of N-acetylcarnosine acting as the ophthalmic prodrug of L-carnosine, and depends on the nature of the specific drug delivery lubricant eye-drop formulation applied as the topical solution. The research highlights findings in N-acetylcarnosine prodrug activation, transport mechanisms, drug-to-drug interactions, and formulations in order to unlock the optimization of complicated ocular pharmacology of N-acetylcarnosine. Patented N-acetylcarnosine lubricant eye-drop formula was marketed as numerous human biological brands reaching important distribution networks on over 550 000 bottles sold. Nature Does Nothing Uselessly. -Aristotle

MeSH terms

  • Adhesiveness
  • Administration, Ophthalmic
  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology
  • Biological Availability
  • Carnosine / administration & dosage
  • Carnosine / analogs & derivatives*
  • Carnosine / pharmacokinetics
  • Carnosine / pharmacology
  • Chemistry Techniques, Analytical / methods
  • Clinical Trials as Topic
  • Drug Delivery Systems*
  • Drug Design
  • Humans
  • Ophthalmic Solutions
  • Oxidation-Reduction
  • Prodrugs


  • Antioxidants
  • Ophthalmic Solutions
  • Prodrugs
  • N-acetylcarnosine
  • Carnosine