Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB

Abstract

The blood-brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

Keywords: BBB; SLN; nano drug delivery; neurological disorders.

Figure 1

Blood brain barrier detailed anatomy showing capillary, tight junction, endothelial cell, pericyte, basal lamina, and astrocyte.

Figure 2

Different brain delivery strategies showing the major routes: local delivery, intranasal delivery, and systemic delivery.

Figure 3

Highlighting the utilities of SLNs and their modifications such as: encapsulation of hydrophilic and lipophilic drugs, capable to cross the BBB for target specific drug delivery due to their unique physicochemical nature, can bypass RES system, reduce systemic toxicity, sustained or controlled drug release in a time dependent manner, and can be scaled up in a cost-effective way.

Figure 4

BBB showing individual components and how the drug loaded SLNs can cross the BBB by different physiological mechanisms such as: Paracellular pathway and passive transmembrane diffusion; Protein mediated transport; Receptor-mediated transcytosis (RMT); and Adsorptive-mediated transcytosis (AMT).

Figure 5

Methods to improve SLNs for brain drug delivery: coating with surfactant; surface functionalization; cationization; size modification.

Figure 6

Different representative models for SLNs showing the drug distribution in the lipid core: Drug enriched core model, Drug enriched shell model, Homogenous matrix model.

Figure 7

The procedure of high shear/high speed/ultrasonication homogenization.

Figure 8

The procedure of hot homogenization and cold homogenization.

Figure 9

The procedure of emulsification solvent diffusion/evaporation.

Figure 10

The procedure of microemulsion technique.

Figure 11

The procedure of supercritical fluid technique.

Figure 12

The procedure of spray drying technique.

Figure 13

The procedure of double emulsion technique.

Figure 14

Representation of SLNs applications in CNS in various types of Neurodegenerative disorders.