Lipid and Polymeric Nanoparticles: Successful Strategies for Nose-to-Brain Drug Delivery in the Treatment of Depression and Anxiety Disorders

Abstract

Intranasal administration has gained an increasing interest for brain drug delivery since it allows direct transport through neuronal pathways, which can be quite advantageous for central nervous system disorders, such as depression and anxiety. Nanoparticles have been studied as possible alternatives to conventional formulations, with the objective of improving drug bioavailability. The present work aimed to analyze the potential of intranasal nanoparticle administration for the treatment of depression and anxiety, using the analysis of several studies already performed. From the carried-out analysis, it was concluded that the use of nanoparticles allows the drug's protection from enzymatic degradation, and the modulation of its components allows controlled drug release and enhanced drug permeation. Furthermore, the results of in vivo studies further verified these systems' potential, with the drug reaching the brain faster and leading to increased bioavailability and, consequently, therapeutic effect. Hence, in general, the intranasal administration of nanoparticles leads to a faster onset of action, with increased and prolonged brain drug concentrations and, consequently, therapeutic effects, presenting high potential as an alternative to the currently available therapies for the treatment of depression and anxiety.

Keywords: anxiety; depression; intranasal; nanoparticles; nose-to-brain.

Figure 1

Pathways of brain drug transport after intranasal administration: direct transport (neuronal transport—olfactory nerve and trigeminal nerves) and indirect transport (systemic distribution).

Figure 2

Main types of nanometric systems: liposomes, nanoemulsions, polymeric nanoparticles, and lipid nanoparticles.

Figure 3

Summary of the ideal nanoparticle formulation characteristics for intranasal administration.

Figure 4

(A)—Schematic representation of the making of icariin nanogels; (B)—Immobility duration in a forced swimming test, (C)—Immobility duration in tail suspension test, and (D)—Total distance travelled in open field test, in mice, after intranasal administration of saline buffer (negative control), oral administration of a fluoxetine solution (Fluo, positive control), intranasal administration of the icariin nanogel (NGSTH), or oral administration of an icariin solution; (E)—Changes in body weight, and (F)—Changes in 1% sucrose preference, in rats, after no administration (CUMS) or intranasal administration of saline buffer (negative controls), oral administration of a fluoxetine solution (Fluo, positive control), intranasal administration of the icariin nanogel (NGSTH), or oral administration of an icariin solution; ## p < 0.01, compared with the negative control group; adapted from Xu et al. [54], reproduced with permission from Elsevier [License Number 5426000092048].

Figure 5

(A)—Desvenlafaxine brain concentration after intranasal administration of a drug solution (DVF (i.n.)) or the developed nanoparticles (DVF NPs i.n.), or the intravenous administration of the nanoparticles (DVF NPs (i.v.)); (B)—Evaluation of the antidepressant activity of intranasal desvenlafaxine nanoparticles (DVF NPs (i.n.)), intranasal desvenlafaxine solution (DVF (i.n.)) and oral desvenlafaxine solution (DVF (Oral)), in chronically depressed rats; (C)—Effect of intranasal desvenlafaxine nanoparticles (DVF NPs (i.n.)), intranasal desvenlafaxine solution (DVF (i.n.)) and oral desvenlafaxine solution (DVF (Oral)) on neurotransmitter levels in rat brain; ¶ and * represent p < 0.05, ¶¶ and ** represent p < 0.01; Conc.—concentration; DVF—desvenlafaxine; NPs—nanoparticles; adapted from Tong et al. [61], reproduced with permission from Elsevier [License Number 5426000412295].

Figure 6

(A)—Scanning electron microscope images of the buspirone chitosan nanoparticles (on the left (2.c.(i))) and thiolated chitosan nanoparticles (on the right (2.c.(ii))); (B)—Ex vivo permeation study of buspirone chitosan nanoparticles (Chitosan NPs), thiolated chitosan nanoparticles (Thiolated chitosan NPs), and drug solution (Plain drug); (C)—Buspirone brain and blood concentrations after intranasal administration of the thiolated chitosan nanoparticles; BUH—buspirone; conc—concentration; NPs—nanoparticles; adapted from Bari et al. [64], reproduced with permission from Elsevier [License Number 5426000697685].