Pharmacokinetics and Pharmacodynamics of Intranasal Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Nose-to-Brain Delivery

Abstract

Nose-to-brain drug delivery has been of great interest for the treatment of many central nervous system (CNS) diseases and psychiatric disorders over past decades. Several nasally administered formulations have been developed to circumvent the blood-brain barrier and directly deliver drugs to the CNS through the olfactory and trigeminal pathways. However, the nasal mucosa’s drug absorption is insufficient and the volume of the nasal cavity is small, which, in combination, make nose-to-brain drug delivery challenging. These problems could be minimized using formulations based on solid lipid nanoparticles (SLNs) or nanostructured lipid carriers (NLCs), which are effective nose-to-brain drug delivery systems that improve drug bioavailability by increasing drug solubility and permeation, extending drug action, and reducing enzymatic degradation. Various research groups have reported in vivo pharmacokinetics and pharmacodynamics of SLNs and NLCs nose-to-brain delivery systems. This review was undertaken to provide an overview of these studies and highlight research performed on SLN and NLC-based formulations aimed at improving the treatment of CNS diseases such neurodegenerative diseases, epilepsy, and schizophrenia. We discuss the efficacies and brain targeting efficiencies of these formulations based on considerations of their pharmacokinetic parameters and toxicities, point out some gaps in current knowledge, and propose future developmental targets.

Recent Advances in Intranasal Liposomes for Drug, Gene, and Vaccine Delivery

“…In PK studies, the maximum drug concentration (C max ) and area under the concentration–time curve (AUC plasma and AUC brain ) were calculated and compared among formulations. Different parameters to evaluate the brain-targeting efficacy of the liposomes, such as drug targeting efficiency (DTE), drug transport percentage (DTP), B IN/IV , and RB, are calculated as follows [ 87 , 88 ]. …”

“…Some respiratory cells are covered with cilia, which play a primary role in mucociliary clearance that protects the respiratory tract from pathogens or particles [ 100 ]. In this region, the ophthalmic and maxillary branches of the trigeminal nerves are responsible for the transport of drugs and genes directly to the brain [ 87 ].…”

“…Drugs and genes in the nasal cavity are distributed to the olfactory region, from where they can be transported to the brain mainly via an extraneuronal route along olfactory neurons in only a few minutes. This is the primary mechanism of the nose-to-brain transport of IN drugs and genes [ 87 , 101 ]. Other mechanisms occurring in the olfactory region include intraneuronal olfactory neuron endocytosis, supporting cell endocytosis, and intercellular transport across tight junctions, which may be time-consuming [ 105 ].…”

“…Other mechanisms occurring in the olfactory region include intraneuronal olfactory neuron endocytosis, supporting cell endocytosis, and intercellular transport across tight junctions, which may be time-consuming [ 105 ]. Drugs and genes can also be transported to the brain via the trigeminal nerve pathway by the extraneuronal and intraneuronal routes [ 87 ]. There is also an indirect pathway to deliver drugs and genes to the brain, through which the drugs and genes first enter systemic circulation after IN administration, cross the BBB, and reach the brain.…”

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

“…A large number of antiretroviral therapeutic molecules from various categories have been approved by the United States Food and Drug Administration (US FDA) for the treatment of neuroAIDS [ 2 ]. Many formulation strategies have been assessed to deliver these therapeutics to provide direct nose-to-brain delivery [ 16 , 17 ]. Drops, sprays, gels, powders, inserts, ointments, and other nasal preparations are utilized to transport the medicine to the target site, the brain [ 13 ].…”