Characterization of alkanoyl-10-O-minocyclines in micellar dispersions as potential agents for treatment of human neurodegenerative disorders

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Antonio Di StefanoFrancesco Barbato

Abstract

Minocycline is a widely used antibacterial agent. Moreover, it is also demonstrated to be effective in several neurodegenerative disorders, due to its antioxidant and anti-inflammatory activities. However, the last activity is only apparent at very high doses. In fact, minocycline poorly crosses the blood-brain barrier (BBB) due to its low lipophilicity and half-life. The present work details the physicochemical characterization of a series of alkanoyl-10-O-minocycline derivatives (2-6), which are able to produce self-assembled aggregates in aqueous solution. The n-octanol/aqueous phase lipophilicity of minocycline and its derivatives were assessed by theoretical calculation, by shake-flask method, and by reversed-phase HPLC. Moreover, we determined their affinity for membrane phospholipids measuring their HPLC retention on phospholipid-based stationary phases, the so-called "Immobilized Artificial Membranes" (IAMs). Our results indicate high lipophilicity values for the minocycline derivatives (compounds 2-6); these values and the corresponding phospholipid affinities increase with the length of the hydrocarbon moiety substituent. Furthermore, the ability of the investigated alkanoyl-10-O-minocycline derivatives to self-assemb...Continue Reading

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Citations

Nov 17, 2010·Amino Acids·Francesco PinnenAntonio Di Stefano
Sep 6, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Piera SozioAntonio Di Stefano
Jan 17, 2016·International Journal of Pharmaceutics·Alexander Dontsios HolmkvistJens Schouenborg
Apr 17, 2013·International Journal of Biological Macromolecules·Kalpana NagpalDinanath Mishra
Nov 26, 2009·Macromolecular Bioscience·Ghareb Mohamed SolimanFrançoise M Winnik

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