Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation

Abstract

Contemporary trends in combinatorial chemistry and the design of pharmaceuticals targeting brain disorders have favored the development of drug candidates with increased lipophilicity and poorer water solubility, with the expected improvement in delivery across the blood–brain barrier (BBB). The growing availability of innovative excipients/ligands allowing improved brain targeting and controlled drug release makes the lipid nanocarriers a reasonable choice to overcome the factors impeding drug delivery through the BBB. However, a wide variety of methods, study designs and experimental conditions utilized in the literature hinder their systematic comparison, and thus slows the advances in brain-targeting by lipid-based nanoparticles. This review provides an overview of the methods most commonly utilized during the preclinical testing of liposomes, nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers intended for the treatment of various CNS disorders via the parenteral route. In order to fully elucidate the structure, stability, safety profiles, biodistribution, metabolism, pharmacokinetics and immunological effects of such lipid-based nanoparticles, a transdisciplinary approach to preclinical characterization is mandatory, covering a comprehensive set of physical, chemical, in vitro and in vivo biological testing.

Biobased nanoemulsions for targeted drug delivery to treat dementia and aging

“…The use of lipid nanocarriers, such as nanoemulsions, to circumvent the barriers that prevent medication transport across the BBB has very recently brought these materials back into the spotlight. As reviewed by Ilic et al (in 2023) [53], among the various strategies studied to overcome the low-water-solubility of various central nervous system (CNS)-active drugs as well as surmount the obstacles in BBB crossing, lipid-based nanoparticles have been recognized as an excellent platform for brain targeting. Conventional dosage forms are associated with a lack of targetabiliity, often resulting in low concentrations within the brain and, hence, a suboptimal therapeutic outcome [53].…”

“…As reviewed by Ilic et al (in 2023) [53], among the various strategies studied to overcome the low-water-solubility of various central nervous system (CNS)-active drugs as well as surmount the obstacles in BBB crossing, lipid-based nanoparticles have been recognized as an excellent platform for brain targeting. Conventional dosage forms are associated with a lack of targetabiliity, often resulting in low concentrations within the brain and, hence, a suboptimal therapeutic outcome [53]. In contrast, the "HDL-like" lipid nanoemulsion type (also referred to as "LCM/ND nanoemulsions" [3,5,6] ) displays a natural tendency to target SR-BI receptors (cf.…”

Breaking Barriers: A Future Perspective on Glioblastoma Therapy with mRNA-Based Immunotherapies and Oncolytic Viruses

“…However, platforms based on saRNA technology offer a versatile application approach. They can be administered through direct intratumoral injection or adapted to address specific challenges, such as the formidable barrier posed by the blood–brain barrier (BBB) in combatting brain tumors like GBM [ 101 , 102 , 103 ]. Overcoming the selective permeability of the BBB is crucial for effective drug delivery to the central nervous system (CNS).…”

Self-assembled carriers as drug delivery systems: Current characterization challenges and future prospects

“…To name a few, whey protein, chitosan, levan, hyaluronic acid, and heparin, were tested native, in combination (e.g., protein-polysaccharide complexes), and after hydrophobic modifications (usually with octenyl-succinic anhydride, OSA) to enable the encapsulation of hydrophilic and lipophilic actives as well (28,29). This is especially important considering the fact that a number of newly synthetized active ingredients are characterized with poor water solubility (30). Some researchers showed more interest in polysaccharide-based self-assembly systems, such as chitosan.…”