Both intracranial and intravenous administration of functionalized carbon nanotubes protect dopaminergic neuronal death from 6-hydroxydopamine

Abstract

Purpose: Although single-walled nanotubes (SWNTs) with functional groups have been suggested as a potential nanomedicine to treat neuronal disorders, effective routes to administer SWNTs have not been compared thus far. The blood–brain barrier is a considerable challenge for the development of brain-targeting drugs, and therefore functionalized SWNT routes of administration have been needed for testing Parkinson’s disease (PD) treatment. Here, effective administration routes of functionalized SWNTs were evaluated in PD mouse model. Methods: Three different administration routes were tested in PD mouse model. Functionalized SWNTs were injected directly into the lateral ventricle three days before (Method 1) or after (Method 2) 6-hydroxydopamine (6-OHDA) injection to compare the protective effects of SWNTs against dopaminergic neuronal death or functionalized SWNTs were injected intravenously at three and four days after 6-OHDA injection (Method 3). Asymmetric behaviors and histological assessment from all animals were performed at two weeks after 6-OHDA injection. Results: Ventricular injections of SWNTs both before or after 6-OHDA exposure protected dopaminergic neurons both in the substantia nigra and striatum and alleviated rotational asymmetry behavior in PD mice. Moreover, intravenous administration of SWNTs three and four days after 6-OHDA injection also prevented neuronal death and PD mice behavioral impairment without apparent cytotoxicity after six months post-treatment. Conclusion: Our study demonstrates that functionalized SWNTs could effectively protect dopaminergic neurons through all administration routes examined herein. Therefore, SWNTs are promising nanomedicine agents by themselves or as therapeutic carriers to treat neuronal disorders such as PD.