Synthesis and characterization of chitosan-grafted-dopamine based micelles as multifunctional nanomedicines for Parkinson's disease treatment by intranasal administration.
Synthesis and characterization of chitosan-grafted-dopamine based micelles as multifunctional nanomedicines for Parkinson's disease treatment by intranasal administration.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Bari, IT · Author affiliation
Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, via E. Orabona, 4-70125, Bari, Italy. adriana.trapani@uniba.it.Location evidence
Foggia, IT · Author affiliation
Department of Clinical and Experimental Medicine, University of Foggia, 71122, Foggia, Italy.Location evidence
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Original abstract
The main aim of this work was to synthesize new chitosan amphiphilic derivatives able to self-assembly encapsulating substances acting at different target sites implicated in Parkinson disease (PD). For this purpose, O-carboxymethyl-chitosan (O-CMCS) was grafted with dopamine (DA) exploiting a carbodiimide mediated coupling reaction using different polymer/DA weight ratios. The structural characterization of the resulting O-CMCS-g-DA conjugates was carried out by spectral (i.e., ì FT-IR, 1H-NMR spectroscopy) and potentiometric titrations. The physicochemical characterization of these conjugates was performed by thermal analysis, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy. The in vitro DA release was carried out in simulated nasal fluid showing in any case a sustained release of the neurotransmitter. The amphiphilic O-CMCS-g-DA conjugate at highest substitution degree was allowed to form micelles using the dialysis method. The Critical Micellar Concentration of such micelles was determined by the conductometric method and resulted of 1 × 10- 4 mg/mL Quercetin (QUE), selected as hydrophobic antioxidant model drug, was encapsulated into the core of these micelles with an efficiency of 18%. From a biological point of view, none of the O-CMCS-g-DA conjugates was cytotoxic against the target neuronal SH-SY5Y cells. Moreover, all the O-CMCS-g-DA conjugates were able to modulate neuroinflammation as demonstrated by mRNA expression level analysis. Therefore, these O-CMCS-g-DA based micelles showed a great potential as multifunctional nanomedicines for brain delivery by intranasal route of a lipophilic antioxidant involved in the oxidative stress together with the neurotransmitter DA exploiting a delivery system with modulating properties of neuroinflammation.