Preparation of a novel ginkgolide B niosomal composite drug

Abstract

Ginkgolide B (GB) and Puerarin (Pue) are active pharmaceutical ingredients for the treatment of Parkinson’s disease (PD); however, both are poorly water-soluble, which limits their bioavailability. The present study used the niosome vesicle encapsulation technique to prepare a novel GB composite drug. The conditions for GB–Pue niosomal complex preparation were as follows: a hydration temperature of 60°C, a hydrophilic–lipophilic balance of 10.5, a drug–carrier mass ratio of 8:100, and a surfactant–cholesterol mass ratio of 1.5:1. The niosomal complex suspension was uniformly distributed and milky white in color, with no stratification over a duration of 1 month. It had an average particle size of 187.3 nm, a particle-size distribution of 0.237, a GB encapsulation efficiency (EE) of 68.2%, a GB drug-loading rate of 90.1%, a Pue EE of 40.5%, and a Pue drug-loading rate of 83.3%. The optimal storage temperature for the niosomal complex suspension was 4°C. Following an intravenous injection of the niosomal complex suspension into the rat tail, the area under the curve (AUC) from 0 to 4 h was 54.1 h µg mL−1, with a mean residence time (MRT) of 0.96 h, a distribution half-life (T1/2α) of 0.195 h, and a total clearance of 0.003 L h−1 kg−1. The AUC and MRT of the composite prescription were 1.1- and 1.4-times those of the commercial injection, respectively, showing significantly increased sustained release and bioavailability. Moreover, the distribution of GB in the brain tissue was 1.8-times that of the commercial injection. In conclusion, the novel GB niosomal composite drug, with excellent stability, improved pharmacokinetics, and brain tissue distribution, demonstrates great potential for the delivery of GB and Pue for PD therapeutics.

Liposome-Derived Nanosystems for the Treatment of Behavioral and Neurodegenerative Diseases: The Promise of Niosomes, Transfersomes, and Ethosomes for Increased Brain Drug Bioavailability

“…Ginkgolide B, a diterpene extracted from Ginkgo biloba, has been proven to have potential for the treatment of Alzheimer's disease, since by having an inhibiting role on the platelet-activating factor, it has been shown to protect neuronal cells that were damaged by Aβ accumulation from further harm. Additionally, this compound has also been shown to reduce the apoptosis induced by the Aβ peptide via the brain-derived neurotrophic factor mechanism, and to have reparative and protective effects on Aβ peptide-damaged mitochondria [115,[170][171][172]. Moreover, ginkgolide B also appears to be promising in Parkinson's disease-related pathophysiology factors, since it was proved to regulate the D-glutamic acid pathway, hence affecting glutamic acid and dopamine metabolism, which are connected to the early stages of this disease [115,173,174].…”

“…Additionally, this compound has also been shown to reduce the apoptosis induced by the Aβ peptide via the brain-derived neurotrophic factor mechanism, and to have reparative and protective effects on Aβ peptide-damaged mitochondria [115,[170][171][172]. Moreover, ginkgolide B also appears to be promising in Parkinson's disease-related pathophysiology factors, since it was proved to regulate the D-glutamic acid pathway, hence affecting glutamic acid and dopamine metabolism, which are connected to the early stages of this disease [115,173,174]. On the other hand, puerarin, an isoflavone extracted from Pueraria genus plants, has also proven to have potentially beneficial effects in both Alzheimer's and Parkinson's disease, due to its antioxidant properties (free radical scavenging, and endogenous antioxidant activity increase), regulation of calcium signaling pathways, functional stabilization of amino acid neurotransmitters and maintenance of the dynamic balance between them (excitatory vs. inhibitory), and regulation of neuronal apoptosis and overall cell damage.…”

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

“…Functional “inner and outer” drug fiber membranes can also be used to regenerate tissue [ 179 ]. Additionally, the dioleyl phosphatidic acid (DOPA) carrier wrapped puerarin 5-FU formed biodegradable polymer nanoparticles, and novel puerarin nanoemulsion (nanoPue), pegylated nanoparticles, GO-based nanoplatform, and vesicular encapsulation technology-based GB-PUE-ribosome complex intravenous injection preparations can also improve the efficacy of puerarin [ 180 , 181 , 182 , 183 , 184 ].…”

Impacts of Drug Interactions on Pharmacokinetics and the Brain Transporters: A Recent Review of Natural Compound-Drug Interactions in Brain Disorders

“…Borneol, a bicyclic monoterpene that exerts anti-inflammatory and antiepileptic activities, possesses BBB permeability-enhancing effect by inhibiting P-gp and MRPs in the BBB and disassembling TJ proteins, reversibly [ 106 ]. Recent studies reported that borneol-modified nanoparticles and niosomes could enhance the brain uptake of loaded drugs, dopamine, and ginkgolide B and puerarin, respectively, compared to the plane nanoparticle and plane niosomes, thereby exerting more potent therapeutic effects in Parkinson’s disease-induced model [ 107 , 108 ].…”