Table 1.

Characteristics of lipid-based nanocarriers to improve nose-to-brain drug delivery.

Lipid-based nanocarrier	General characteristic to improve drug delivery	Specific characteristic to improve nose-to-brain drug delivery	Ref.
1. Lipid nanoparticles	•Colloidal dispersions of solid particles with 0.1 up to 30% w/w of lipid(s), stabilized by one or two emulsifiers with a concentration range from 0.5% to 5% w/w; •Ability to encapsulate poor-water soluble drugs; •Industrial scale manufacture facility at low cost; •Good physical-chemical stability; •Improved drug bioavailability; •Ability for drug targeting; •Drug protection; •Prolonged drug release; •Use of generally recognised as safe (GRAS) excipients; •Low or no toxicity of formulations.	•Allow the direct transport to the brain via trigeminal and olfactory nerves; •Improve bioavailability of drugs in the brain; •Ability for drug targeting; •Use of physiological lipids and GRAS excipients, providing high biocompatibility with the nasal mucosa and, therefore, low or no toxicity; •Ability to adhere to the olfactory epithelium; •Prolong the contact time of the formulation on the nasal mucosa, avoiding the fast mucociliary clearance; •Drug protection from nasal enzymatic degradation; •Prolonged drug release.	39, 40, 41, 42
1.1. Solid lipid nanoparticles (SLNs)	•1st generation of lipid nanoparticles; •Nanoparticles contain a lipophilic core composed by one solid lipid.		40, 43, 44
1.2. Nanostructured lipid carriers (NLCs)	•2nd generation of lipid nanoparticles; •Nanoparticles contain a lipophilic core formed by a mixture of one solid lipid (in bigger quantity) with one liquid lipid (in less quantity).		40, 45, 46
2. Nanoemulsions (NEs)	•Heterogeneous and thermodynamically unstable systems composed by an oily and a water phase, stabilized by emulsifier(s); •Oil-in-water (o/w) NE are more common and have ability to transport lipophilic molecules; •Droplet sizes lower than 500 nm; •Industrial scale production facility at low cost; •Good physical-chemical stability; •Improved drug bioavailability; •Ability for drug targeting; •Drug protection; •Prolonged drug release; •Use of physiological lipids and GRAS excipients; •Low or no toxicity of formulations.		47