L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine

Stavroula G Nanaki; Konstantinos Spyrou; Pelagia Veneti; Niki Karouta; Dimitrios Gournis; Turki N Baroud; Panagiotis Barmpalexis; Dimitrios N Bikiaris

doi:10.3390/polym14194004

L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine

Polymers (Basel). 2022 Sep 24;14(19):4004. doi: 10.3390/polym14194004.

Authors

Stavroula G Nanaki¹, Konstantinos Spyrou², Pelagia Veneti¹, Niki Karouta², Dimitrios Gournis², Turki N Baroud³, Panagiotis Barmpalexis⁴, Dimitrios N Bikiaris¹

Affiliations

¹ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Department of Materials Science and Engineering, University of Ioannina, 45110 Ioannina, Greece.
³ Materials Science and Engineering, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi Arabia.
⁴ Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Abstract

The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via ¹H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS's utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil-water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release studies revealed that the prepared NPs could prolong GAL's release for up to 12 days. In sum, regarding the most promising system, the results of the present study clearly suggest that the preparation of NPs using both Cys-CS and CDs results in a more thermodynamically stable drug dispersion, while a zero-order release profile was achieved, which is essential to attain a stable in vivo pharmacokinetic behavior.

Keywords: L-cysteine; carbon dots; drug delivery; galantamine; modified chitosan; nanoparticles; porous carbon nanostructures.

Grants and funding

1914/This project has received funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No [1914].