Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application

Background: The blood-brain barrier (BBB) bypass of dopamine (DA) is still a challengefor supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugshave been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore,the aim of this work is the synthesis and preliminary characterization of an oxidized alginatedopamine(AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff basewas designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA werecharacterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesiveand release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesivematerial among the tested ones and it released the neurotransmitter in simulated nasal fluidand in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanningnear-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescentlylabeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastomacell line up to 100 ?g/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h.Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encouragefurther ex vivo and in vivo studies in view of nose-to-brain administration.