Pegylated Gold Nanospheres Conjugated with Cyclodextrins are Delivered to the Brain after Intranasal Administration in Rats

Abstract

Gold nanospheres (GNS) and cyclodextrins (CD) have been extensively researched for their promising roles in drug delivery. GNS can be effectively functionalized with a range of molecules, serving as versatile carriers for biomedical applications. Meanwhile, CD may form inclusion complexes with diverse drugs, increasing their permeability through cellular membranes. On the other hand, intranasal administration is a non-invasive route for drug delivery that has shown potential for targeting the central nervous system (CNS), bypassing the blood-brain barrier, and allowing the direct delivery of drugs to the brain. In the present report, GNS were multifunctionalized with HS-PEG-OMe/HS-PEG-COOH (GNS-PEGs) and CD to evaluate their potential as drug-delivery platform to the CNS after intranasal administration in rats. The colloidal stability of GNS-PEGs was proved under different conditions and physicochemical characterization confirmed the functionalization of GNS-based nanosystems. The degree of functionalization of GNS with different amounts of CD (GNS-PEGs-CD) was determined by a fluorescamine assay, showing no significant differences among the concentrations used in this report. GNS-based nanosystems did not show cytotoxic effects on SH-SY5Y and bEnd.3 cell lines at the range of concentrations assayed. Finally, while cellular in vitro assay demonstrated that the incorporation of CD significantly improves the nanosystems cell adhesion-internalization, in vivo evaluation showed that GNS-PEGs-CD accumulates in the brain after a single intranasal administration. Overall, this report showed for the first time that GNS functionalized with PEGs and CD may reach the CNS after intranasal administration in Sprague-Dawley rats, which might represent a promising approach for targeted drug delivery to the CNS.

Note:
Funding declaration: This work was financially supported by: Karen Bolaños acknowledges to Postdoctoral ANIDFONDECYT (3220587). Eyleen Araya gives thanks to ANID-FONDECYT (1230303). Claudia Yáñez gives thanks to ANID-FONDECYT (1200592). Marcelo J. Kogan gives thanks to the ANIDFONDECYT (1211482), ANID-FONDAP (15130011 and Apoyo 1523A0008), FONDEQUIP (EQM170111), and Anillo ACT (210068).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval: All animal treatments and experiments were performed following the Guidelines for Care and Use of Laboratory Animals of the University of Chile and approved by the Animal Ethics Committee of this University (17013-CYQ-UCH).

Keywords: Gold nanoparticles, Cyclodextrin, Intranasal administration, Central nervous system, Nose-to-brain delivery