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Parkinson's disease (PD) is a serious neurodegenerative disease wherein the progressive destruction of dopaminergic neurons results in a series of related movement disorders. Effective oral delivery of anti-Parkinson's drugs is challenging owing to the blood-brain barrier (BBB) and the limited plasma exposure. However, polymeric nanoparticles possess great potential to enhance oral bioavailability, thus improving drug accumulation within the brain. In this work, biodegradable poly(ethylene glycol)-b-poly(trimethylene carbonate) (PEG-PTMC) nanoparticles (PPNPs) were developed to deliver Ginkgolide B (GB) as a potent treatment for PD, aiming to enhance its accumulation within both the blood and the brain. The resultant GB-PPNPs were able to facilitate sustained GB release for 48 h and to protect against 1-methyl-4-phenylpyridine (MPP+)-induced neuronal cytotoxicity without causing any toxic damage. Subsequent pharmacokinetic studies revealed that GB-PPNPs accumulated at significantly higher concentrations in the plasma and brain relative to free GB. Oral GB-PPNP treatment was also linked to desirable outcomes in an animal model of PD, as evidenced by improvements in locomotor activity, levels of dopamine and its metabolites, and tyrosine hydroxylase activity. Together, these data suggest that PPNPs may represent promising tools for the effective remediation of PD and other central nervous system disorders. [ABSTRACT FROM AUTHOR]

Acid-base homeostasis is crucial for numerous physiological processes. Na + / HCO 3 − cotransporters (NBCs) belong to the solute carrier 4 (SLC4) family, which regulates intracellular pH as well as HCO 3 − absorption and secretion. However, knowledge of the structural functions of these proteins remains limited. Electrogenic NBC (NBCe-1) is thought to be the primary factor promoting the precise acid–base equilibrium in distinct cell types for filtration and reabsorption, as well as the function of neurons and glia. NBC dysregulation is strongly linked to several diseases. As such, the need for special drugs that interfere with the transmission function of NBC is becoming increasingly urgent. In this review, we focus on the structural and functional characteristics of NBCe1, and discuss the roles of NBCe1 in the kidney, central nervous system (CNS), and related disorders, we also summarize the research on NBC inhibitors. NBCe1 and the related pathways should be further investigated, so that new medications may be developed to address the related conditions. [ABSTRACT FROM AUTHOR]