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

Thi-Thao-Linh Nguyen,Han-Joo Maeng

doi:10.3390/pharmaceutics14030572

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.

Highlights

By analysis of PK parameters, this review provides an insight into the brain targeting efficacies of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)-based formulations and identifies their limitations
After identification and screening steps, 86 articles were included to conduct this systematic review. Some of these articles performed in vivo studies on the same SLN or NLC formulations, and these articles were based on the results of 81 studies
Some of these articles performed in vivo studies on the same SLN or NLC formulasizes, polydispersity indices, and zeta potentials ofsame

Summary

Introduction

Several lipid-soluble molecules can enter the brain by passive diffusion In this mechanism, the molecule lipophilicity generally defines the penetration rate and extent into the brain. The molecule lipophilicity generally defines the penetration rate and extent into the brain Many of these molecules are usually pumped back to the circulatory system by some efflux pumps expressed in the BBB. Small polar molecules, such as amino acids, glucose, nucleosides, and organic anions and cations, are transported by carrier-mediated transport. Another mechanism is receptor-mediated transcytosis, which transports large molecules, such as iron, insulin, and leptin [4]. Only a small number of hydrophobic and low molecular weight molecules can cross the BBB, whereas others are restricted by the barrier characteristics of the BBB, which makes it difficult to develop drugs that target the brain [7]

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