Protein unbound pharmacokinetics of ambroxol in the blood and brains of rats and the interaction of ambroxol with Polygala tenuifolia by multiple microdialysis

Yang, Chao Nan; Peng, Wen Ya; Lin, Lie Chwen; Tsai, Tung Hu

doi:10.1016/j.jep.2020.113764

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…With free Pt acetone solution as control, in vitro release of Pt from F-Pt/M formulation was studied by the dialysis method (Khan et al., 2020 ; Rubab et al., 2021 ; Yang et al., 2021 ). Briefly, 1 mL of samples, equivalent to 0.8 mg drug, were filled into dialysis bags (molecular weight cutoff: 3500 Da) and dialyzed against 1,000 mL of phosphate buffer solution of pH values 7.4 (containing 0.3% Tween 80) to mimic drug release in normal tissues/blood.…”

Section: Methodsmentioning

confidence: 99%

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Increased brain uptake of pterostilbene loaded folate modified micellar delivery system

Wang

Yang

et al. 2022

Drug Delivery

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Effective chemotherapy for clinical treatment of brain diseases is still lacking due to the poor penetration of the blood-brain barrier (BBB). The aim of this study was to construct a folate modified pterostilbene (Pt) loaded polymeric micellar delivery system (F-Pt/M) with mPEG-PCL as carrier material to aim at penetrating the BBB for brain tissue targeting via receptor-mediated endocytosis. In this study, F-Pt/M was prepared using thin-film hydration method and then optimized by response surface methodology (RSM) with the entrapment efficiency (EE), drug loading (DL) and hydrodynamic diameter (HD) as indexes. The average hydrodynamic diameter and zeta potential of optimal F-Pt/M were 133.2 nm and 24.6 mV, respectively. DL (18.3%) and EE (98.6%) made the solubility of Pt in water about 25 times higher than that of crude Pt. Results of DSC evaluation revealed that drugs were successfully encapsulated inside the polymeric micelles. TEM images showed that homogeneous spherical micellar structures with a narrow size distribution were developed. The release result in vitro showed that F-Pt/M presented sustained release behavior compared to control free Pt solution. Compared to non-targeted Pt/M, F-Pt/M had a significantly higher cytotoxicity against FR-overexpressing A172 cells. In vitro cellular uptake tests illustrated that the micellar delivery system could significantly improve the accumulation of drugs in target cells via receptor-mediated endocytosis. BBB penetration value (P) of F-Pt/M was about 4 folds higher than that of free Pt group. In addition, drug targeting index (DTI) was calculated to determine targeting of F-Pt/M to the brain which was found to be 4.89, implying improved brain targeting was achieved. Hence, the developed F-Pt/M exhibited great potential for delivering more drug molecules across the BBB for the treatment of brain diseases.

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Section: Methodsmentioning

confidence: 99%

“…Pharmacokinetic parameters, such as C max (maximum drug concentration), T max (the time to C max ) and AUC 0-t (area under plasma concentration-time curve), were calculated by DAS 2.0 (Drug and Statistics ver 2.0, China). To examine the blood-brain barrier penetration (P) of Pt, the following formula was employed (Yang et al., 2021 ): …”

Section: Methodsmentioning

confidence: 99%

Increased brain uptake of pterostilbene loaded folate modified micellar delivery system

Wang

Yang

et al. 2022

Drug Delivery

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“… 5 , 6 Microdialysis and ultra-high performance liquid chromatography coupled with mass spectrometry found that ambroxol easily penetrates the striatum of rats even at low dosages. 7 Studies in mice and humans have also found therapeutic ambroxol concentrations in the brain. 8 , 9 These properties, together with its low-toxicity profile, make ambroxol an optimal candidate for drug-repurposing.…”

Section: Introductionmentioning

confidence: 99%

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

Patzwaldt

Berezhnoy

Ionescu

et al. 2023

Brain Communications

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Ambroxol is a well-known mucolytic expectorant, which has gained much attention in Amyotrophic lateral sclerosis, Parkinson’s and Gaucher’s disease. A specific focus has been placed on Ambroxol’s glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson’s disease. However, Ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that Ambroxol could have a direct impact on neuronal rescue if administered directly after ischemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, edema, white matter integrity, resting state functional magnetic resonance imaging and behavior for one month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex-vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic edema, reduced white matter degeneration, reduced necrosis, improved behavioral outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post stroke proposes several metabolites that are capable of minimizing post-ischemic damage and that presented prominent shifts during Ambroxol treatment in comparison to controls. Taking everything together, we propose that Ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of Ambroxol administration following stroke onset reduced ischemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

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“…AMB (trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol) is an active ingredient used in the chronic bronchitis prevention (Xu et al, 2015); for complications, such as bronchopulmonary diseases in new borns, hyaline membrane diseases and in antioxidant therapies. Various analytical techniques have been reported for AMB titration in both biological and pharmaceutical samples using liquid chromatography , gas chromatography (Yang et al, 2021), chromatography with amperometric detection (Erady et al, 2019), UV spectrophotometry (Yang et al, 2021) and voltammetry (Zhu et al, 2021). In contrast, little is known regarding its environmental behavior, its degradation (Brüggemann et al, 2003), interaction with other environmental media and extraction method from wastewaters (Beckers et al, 2018;Brüggemann et al, 2003;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

High efficiency photocatalytic degradation of Ambroxol over Mn doped TiO2: Experimental designs, identification of transformation products, mineralization and mechanism

Tab

Dahmane

Belabed

et al. 2021

Science of The Total Environment

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Ambroxol (AMB) is a drug commonly used for chronic bronchitis prevention. Once released in surface water, this recalcitrant chemical becomes a hazardous pollutant.Here, we investigated the ability of 1% Mn-doped TiO 2 (Mn-TiO 2 ) to mineralize AMB by photocatalysis. We studied the morphology, and the physical and electrochemical properties of Mn-TiO 2 using X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy, X-ray fluorescence, BET method, UV-visible, and electrochemical study and optimized the AMB degrading experimental conditions through response surface methodology (RSM). Mn-TiO 2 at the dose of 0.625 g.L -1 allowed the complete photodegradation of AMB (30 ppm) at pH 7 under UVA light irradiation for 30 min while total mineralization in CO 2 (> 96%) was achieved after 24 h of irradiation. Mn-TiO 2 was 1.6-time more efficient than TiO 2 Degussa P25. Product studies were also carried out by liquid 2 chromatography coupled to electrospray high resolution mass spectrometry. Twentyone photodegradation products were detected and identified. In addition, ionic chromatography analyses revealed the release of Br -, NH 4 + , and NO 3 at respectively 97, 63 and 35% of the total Br, and N initially present in AMB. Finally, the reusability of the photocatalyst was also tested. After four cycles, the almost complete photodegradation of AMB was achieved showing that Mn-TiO 2 was highly stable.This work brings new physical characteristics on Mn-TiO 2 photocatalyst. Moreover, it is the first study investigating the photocatalytic degradation of recalcitrant AMB drug.

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Protein unbound pharmacokinetics of ambroxol in the blood and brains of rats and the interaction of ambroxol with Polygala tenuifolia by multiple microdialysis

Cited by 8 publications

References 32 publications

Increased brain uptake of pterostilbene loaded folate modified micellar delivery system

Increased brain uptake of pterostilbene loaded folate modified micellar delivery system

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

High efficiency photocatalytic degradation of Ambroxol over Mn doped TiO2: Experimental designs, identification of transformation products, mineralization and mechanism

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