Pharmacokinetics and Tissue Disposition of Nanosystem-Entrapped Betulin After Endotracheal Administration to Rats

Pozharitskaya, Olga N.; Karlina, M. V.; Shikov, Alexander N.; Косман, В. М.; Makarov, Valery G.; Casals, Eudald; Rosenholm, Jessica M.

doi:10.1007/s13318-016-0340-7

Cited by 18 publications

(17 citation statements)

References 14 publications

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“…The pharmacokinetic calculations for fucoidan in organs and plasma were performed with the Excel add-in program PK Solver. The parameters were calculated from the concentration-time data using a noncompartmental pharmacokinetic model as described previously [ 43 ]. The results are expressed as the mean ± standard deviation ( n = 5 for each time point).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats

Pozharitskaya¹,

Shikov²,

Фаустова³

et al. 2018

Marine Drugs

105

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Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC0–t = 10.74 µg·h/g; Cmax = 1.23 µg/g after 5 h), spleen (AUC0–t = 6.89 µg·h/g; Cmax = 0.78 µg/g after 3 h), and liver (AUC0–t = 3.26 µg·h/g; Cmax = 0.53 µg/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats

Pozharitskaya¹,

Shikov²,

Фаустова³

et al. 2018

Marine Drugs

105

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“…Noteworthy, BET exerted a pro-osteogenic effect at the low, non-toxic concentrations. Given the satisfactory bioavailability of BET at the diverse routes of administration [64,65], we can conclude that this compound has the potential to be used as a medicine or supplement in treatment of bone osteoporotic lesions, especially since the recent studies [38] indicated the anti-osteoclastic activity of BET. However, further in vivo studies in animal models are necessary to confirm the potential of BET to enhance osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Betulin Promotes Differentiation of Human Osteoblasts In Vitro and Exerts an Osteoinductive Effect on the hFOB 1.19 Cell Line Through Activation of JNK, ERK1/2, and mTOR Kinases

et al. 2019

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Although betulin (BET), a naturally occurring pentacyclic triterpene, has a variety of biological activities, its osteogenic potential has not been investigated so far. The aim of this study was to assess the effect of BET on differentiation of human osteoblasts (hFOB 1.19 and Saos-2 cells) in vitro in osteogenic (with ascorbic acid as an osteogenic supplement) and osteoinductive (without an additional osteogenic supplement) conditions. Osteoblast differentiation was evaluated based on the mRNA expression (RT-qPCR) of Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), type I collagen-α1 (COL1A1), and osteopontin (OPN). Additionally, ALP activity and production of COL1A1 (western blot analysis) and OPN (ELISA) were evaluated. The level of mineralization (calcium accumulation) was determined with Alizarin red S staining. BET upregulated the mRNA level of RUNX2 and the expression of other osteoblast differentiation markers in both cell lines (except the influence of BET on ALP expression/activity in the Saos-2 cells). Moreover, it increased mineralization in both cell lines in the osteogenic conditions. BET also increased the mRNA level of osteoblast differentiation markers in both cell lines (except for ALP in the Saos-2 cells) in the osteoinductive conditions, which was accompanied with increased matrix mineralization. The osteoinductive activity of BET in the hFOB 1.19 cells was probably mediated via activation of MAPKs (JNK and ERK1/2) and mTOR, as the specific inhibitors of these kinases abolished the BET-induced osteoblast differentiation. Our results suggest that BET has the potential to enhance osteogenesis.

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“…However, betulin and its derivatives have a broad spectrum of biological relevance, thus they have a high potential for application in transdermal systems [ 19 , 20 ]. To date, several formulations containing betulin and its derivatives have been developed [ 21 , 22 , 23 , 24 , 25 ]. However, there are no literature reports describing the penetration of vehicles containing these compounds through the skin.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Antioxidant and Skin Permeation Properties of Betulin and Its Derivatives

et al. 2021

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This study investigated the antioxidant activity DPPH, ABTS, and Folin–Ciocalteu methods of betulin (compound 1) and its derivatives (compounds 2–11). Skin permeability and accumulation associated with compounds 1 and 8 were also examined. Identification of the obtained products (compound 2–11) and betulin isolated from plant material was based on the analysis of 1H- NMR and 13C-NMR spectra. The partition coefficient was calculated to determine the lipophilicity of all compounds. In the next stage, the penetration through pig skin and its accumulation in the skin were evaluated of ethanol vehicles containing compound 8 (at a concentration of 0.226 mmol/dm3), which was characterized by the highest antioxidant activity. For comparison, penetration studies of betulin itself were also carried out. Poor solubility and the bioavailability of pure compounds are major constraints in combination therapy. However, we observed that the ethanol vehicle was an enhancer of skin permeation for both the initial betulin and compound 8. The betulin 8 derivative showed increased permeability through biological membranes compared to the parent betulin. The paper presents the transformation of polycyclic compounds to produce novel derivatives with marked antioxidant activities and as valuable intermediates for the pharmaceutical industry. Moreover, the compounds contained in the vehicles, due to their mechanism of action, can have a beneficial effect on the balance between oxidants and antioxidants in the body, minimizing the effects of oxidative stress. The results of this work may contribute to knowledge regarding vehicles with antioxidant potential. The use of vehicles for this type of research is therefore justified.

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Pharmacokinetics and Tissue Disposition of Nanosystem-Entrapped Betulin After Endotracheal Administration to Rats

Abstract: Entrapment of betulin in nanosystem form shows promise as a novel strategy in the treatment of pulmonary diseases.

Cited by 18 publications

References 14 publications

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats

Betulin Promotes Differentiation of Human Osteoblasts In Vitro and Exerts an Osteoinductive Effect on the hFOB 1.19 Cell Line Through Activation of JNK, ERK1/2, and mTOR Kinases

Enhancement of the Antioxidant and Skin Permeation Properties of Betulin and Its Derivatives

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