RESUMO
The synthesis of graphene-based materials for drug delivery represents an area of active research, and the use of graphene in drug delivery systems is promising due to its unique properties. Thus, in the present work, we discuss the potential of few-layer graphene in a hydrogel system for dopamine release. The hydrogels are frequently used for these systems for their special physico-chemical properties, which can ensure that the drug is effectively released in time. However, the release from such structures is mostly determined by diffusion alone, and to overcome this restriction, the hydrogel can be "improved" with nanoscale fillers like graphene. The release kinetics of the composite obtained were analyzed to better understand how the use of graphene, instead of the more common graphene oxide (GO) and reduced graphene oxide (rGO), affects the characteristics of the system. Thus, the systems developed in this study consist of three main components: biopolymer, graphene, and dopamine. The hydrogels with graphene were prepared by combining two different solutions, one with polyacrylic acid and agarose and one with graphene prepared by the exfoliation method with microwave irradiation. The drug delivery systems were developed by adding dopamine to the obtained hydrogels. After 24 h of release, the presence of dopamine was observed, demonstrating that the system developed can slow down the drug's degradation because of the interactions with the graphene nanoplates and the polymer matrix.
RESUMO
BACKGROUND: The blood-brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have 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 alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. METHODS: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. RESULTS: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 µg/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 encourage further ex vivo and in vivo studies in view of nose-to-brain administration.
