Nanosystems, Drug Molecule Functionalization and Intranasal Delivery: An Update on the Most Promising Strategies for Increasing the Therapeutic Efficacy of Antidepressant and Anxiolytic Drugs

Abstract

Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration, respectively. Nevertheless, treatment is usually given through the oral route, but the low permeability of the blood–brain barrier reduces the amount of drug that will be able to reach it, thus consequently reducing the therapeutic efficacy. Which is why it is imperative to find new solutions to make these treatments more effective, safer, and faster. To overcome this obstacle, three main strategies have been used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways, bypassing the blood–brain barrier and avoiding the hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions, and nanogels; and drug molecule functionalization by ligand attachment, such as peptides and polymers. Pharmacokinetic and pharmacodynamic in vivo studies’ results have shown that intranasal administration can be more efficient in brain targeting than other administration routes, and that the use of nanoformulations and drug functionalization can be quite advantageous in increasing brain–drug bioavailability. These strategies could be the key to future improved therapies for depressive and anxiety disorders.

Formulation, Characterization, and Evaluation of β-Cyclodextrin Functionalized Hypericin Loaded Nanocarriers

“…Several studies have reported that the intranasal route can be a good option as a nose to brain targeting approach for treating the depressive disorders. ,− Trigeminal and olfactory pathways have been considered to be merely the routes via which the brain is linked to the outside environment [ , ]. Drugs with limited oral bioavailability because of substantial metabolism have been studied using this route as a viable alternative. − Additionally, the utilization of this nasal route of administration of medication allows the various therapeutics to avoid the first-pass effect.…”

Intranasal Therapy in Palliative Care

“…The V1 and V2 branches of trigeminal nerve innervate the nasal cavity and transmit drug molecules to the brain stem both intracellularly and extracellularly [ 7 ]. Intranasal administration of the molecules allows them to penetrate brain tissue via the olfactory and trigeminal pathways bypassing the blood-brain-barrier (BBB) [ 25 , 26 ]. This is particularly important because the BBB is a very tight, selectively permeable membrane that helps maintain homeostasis in the CNS environment and protects the CNS from exposure to xenobiotics and toxic substances [ 13 , 14 , 27 ].…”

“…The intranasal administration of intravenous formulations of several drugs (fentanyl, sufentanil, ketamine, hydromorphone, midazolam, haloperidol, naloxone, glucagon) may be an effective alternative to intramuscular or intravenous administration [ 26 ]. In a paper by Lam et al (2020), it was stated that formulations available for intravenous delivery can be used for nasal administration using appropriate devices such as a mucosal atomization device (MAD) [ 2 ].…”

“…In a paper by Lam et al (2020), it was stated that formulations available for intravenous delivery can be used for nasal administration using appropriate devices such as a mucosal atomization device (MAD) [ 2 ]. Nevertheless, creating delivery systems that facilitate the supply of molecules to the appropriate tissue is a rapidly developing area of scientific research [ 1 , 26 , 27 ].…”

“…Some reports compared intranasal and intravenous drug administration in animal models and tissue lines [ 11 , 26 ]. Animal models showed that concentrations in brain tissue may be higher after intranasal administration than after intravenous administration [ 72 ].…”