GABA-containing liposomes: neuroscience applications and translational perspectives for targeting neurological diseases

Abstract

There are multiple challenges for neuropharmacology in the future. Undoubtedly, one of the greatest challenges is the development of strategies for pharmacological targeting of specific brain regions for treatment of diseases. GABA is the main inhibitory neurotransmitter in the central nervous system, and dysfunction of GABAergic mechanisms is associated with different neurological conditions. Liposomes are lipid vesicles that are able to encapsulate chemical compounds and are used for chronic drug delivery. This short review reports our experience with the development of liposomes for encapsulation and chronic delivery of GABA to sites within the brain. Directions for future research regarding the efficacy and practical use of GABA-containing liposomes for extended periods of time as well as understanding and targeting neurological conditions are discussed.

Keywords: GABA; Liposomes; Nervous system; Neurological diseases; Neuroscience.

Figure 1 –

Drawing depicting the PEGylated lipid vesicle (PEG liposomes) releasing GABA in the nervous tissue. Given the relevance of GABA as neurotransmitter in the mammalian central nervous system, GABA-liposomes offer a wide range of potential applications to be explored (see text for details).

Figure 2 –

(a) Time course of changes (means ± SE) in mean arterial pressure (MAP; measured by telemetry) of Wistar rats after bilateral nanoinjection of GABA liposomes (200 nl, n=5) into the dorsomedial hypothalamic region. (b) Sagittal view of the rat brain illustrating the stereotaxic nanoinjection procedure reaching the target region. (c) Frontal view of the dorsomedial hypothalamic region; dots represent approximate injection sites; the target injection site is delimited by bold line as defined by Fontes et al., 2011. GABA liposomes formulation and microinjection procedures performed according to Vaz et al., 2015. *p<0.05 vs. injection of empty liposome (control, n=5), Two-Way ANOVA followed by Bonferroni. ARC, arcuate hypothalamic nucleus; DA, dorsal hypothalamic area; DMC, compact portion of dorsomedial hypothalamic nucleus; DMD, diffuse portion of the dorsomedial hypothalamic nucleus; DMN, dorsomedial hypothalamic nucleus; f, fornix; mt, mamillothalamic tract; LH, lateral hypothalamus; VMH, ventromedial hypothalamic nucleus; III, third ventricle. All procedures conform to the regulation set by the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) revised 1996 and were approved by our local committee for ethics in animal experimentation (protocol number: 150-2010).