Efficient Sustained-Release Nanoparticle Delivery System Protects Nigral Neurons in a Toxin Model of Parkinson’s Disease

Abstract

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.

Pharmacokinetics of ginkgolide B–lyophilized nanoparticles after intravenous injection in rats using liquid chromatography–tandem mass spectrometry

“…Nanocarriers can always increase the solubility of drugs or achieve a certain sustained‐release effect 34 . Soybean phospholipid–stabilized nanosuspension, 35 nanoemulsion, 36 polymeric nanocapsules, 37 and others can be used to improve GB bioavailability, but these nano‐preparations are unstable and require the addition of numerous stabilizers, 38 and there are limited data regarding the PK properties of these formulations in animals 39 . Therefore, we prepared GB‐NPs using an innovative, secure polysaccharide polymer ZY‐010 as its carrier, which exhibited good stability and a sustained‐release effect 22 .…”

Nanostructures in Chinese herbal medicines (CHMs) for potential therapy

“…[134][135][136][137] For the effective treatment of PD, biodegradable polyethylene glycol-B-polytrimethylene carbonate nanoparticles are developed to promote the sustained release of Ginkgolide B for 48 h, and to prevent neuronal cytotoxicity. 57 Some studies have found that CUR-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) can induce adult neurogenesis by activating the classical Wnt/b-catenin pathway, and Cur-PLGA-NPs may treat neurodegenerative diseases, such as Alzheimer's disease (AD), by enhancing the self-repair mechanism of the brain. 58 Rhynchophylline is a significant tetracyclic oxindole alkaloid found in the stems of certain Uncaria species 138 and has the potential to be useful in treating AD.…”

“…To enable Ginkgolide B (GB) to cross the BBB for treating PD, biodegradable poly(ethylene glycol)- b -poly(trimethylene carbonate) (PEG–PTMC) nanoparticles (PPNPs) are used to encapsulate GB (GB-PPNPs), which are found in the plasma and brain in high concentrations, thus improving the related indexes of the animal model of PD. 57 Curcumin (CUR), derived from Curcuma longa , is a neuroprotective agent with poor brain bioavailability. This problem is solved by preparing CUR-encapsulated PLGA nanoparticles, which are internalized into hippocampal neural stem cells to induce neurogenesis, representing a new strategy for treating neurodegenerative diseases.…”

Employ of Anthocyanins in nanocarriers for Nano Delivery: <em>I</em><em>n Vitro</em> and <em>I</em><em>n Vivo</em> Experimental Approaches for Chronic Diseases

“…Among the various alternatives studied, those related to nanotechnology and nanoencapsulation have attracted the greatest interest in many fields, such as in medicine, namely in the prevention, diagnosis, and treatment of numerous diseases through active or passive targeting [166][167][168][169][170]. They are preferred over micro-delivery systems because the latter are more unstable in the physiological environment due to their large particle size, low zeta potential, and encapsulation efficiency [171].…”

“…Therefore, various approaches to nanoencapsulation are currently being investigated for the different routes of administration, including intravenous, nasal, oral, parenteral, intraocular, and dermal topical applications [172]. In addition, most of them can also easily cross the blood-brain barrier, which increases the therapeutic potential of the several molecule(s) [170,173]. This technique can be applied because anthocyanins are able to generate van der Waals and hydrogen bonds as well as hydrophobic interactions with these nanocarriers, which increases their stability [24,26,165].…”