TABLE 2.

Comparison of nanoparticle routes of administration into the brain

Routes of administration	Advantages	Disadvantages	Applications
Systemic	Favorable for diseases or tumors not limited to a single or easily accessible location	Quick clearance, BBB transport	Systemic glioblastoma targeting (Gregory et al., 2020)
Intracerebroventricular	Effective biologic delivery rates, bypasses BBB	Invasive, time-consuming	Dopamine delivery for Parkinson’s disease, siRNA (targeting BACE1 and APP) delivery for Alzheimer’s disease, mRNA delivery to Astrocytes and brain neuronal cells (Monge-Fuentes et al., 2021; Shyam et al., 2015; Tanaka et al., 2018)
Intrathecal	Moderate invasiveness, shortened recovery time, bypasses BBB	Nanoparticle clearance prior to delivery	Chronic pain prevention using NPs targeting neurokinin 1 receptor, delivery of frataxin mRNA for Friedreich’s ataxia (Nabhan et al., 2016; Ramírez-García et al., 2019)
Intranasal	Noninvasiveness, bypasses BBB	Lowest delivery rate	Delivery of BMP4 to target brain tumors, delivery of AntagoNAT for upregulation of brain-derived neurotrophic factor (BDNF; Mangraviti et al., 2016; Padmakumar, Jones, Khorkova, et al., 2021)