Pharmacokinetics, Bioavailability, Excretion and Metabolism Studies of Akebia Saponin D in Rats: Causes of the Ultra-Low Oral Bioavailability and Metabolic Pathway

Background: Akebia saponin D (ASD) has a variety of biological activities and great medicinal potential, but its oral bioavailability is so low as to limit its development. Its pharmacokinetic profiles and excretion and metabolism in vivo have not been fully elucidated. This study was an attempt in this area.Methods: A simple LC-MS/MS method to simultaneously quantify ASD and its metabolites M1∼M5 in rat plasma, feces, urine and bile was established with a negative ESI model using dexketoprofen as the internal standard. Meanwhile, the UPLC-HR/MS system was used to screen all possible metabolites in the urine, feces and bile of rats, as compared with blank samples collected before administration. Absolute quantitative analysis was for M0, M3, M4, and M5, while semi-quantitative analysis was for M1, M2, and Orbitrap data.Results: The AUC0-t values after intravenous administration of 10 mg/kg and intragastrical administration of 100 mg/kg ASD were 19.05 ± 8.64 and 0.047 ± 0.030 h*μg/ml respectively. The oral bioavailability was determined to be extremely low (0.025%) in rats. The exposure of M4 and M5 in the oral group was higher than that of M0 in the terminal phase of the plasma concentration time profile, and ASD was stable in the liver microsome incubation system of rats, but metabolism was relatively rapid during anaerobic incubation of intestinal contents of rats, suggesting that the low bioavailability of ASD might have been attributed to the poor gastrointestinal permeability and extensive pre-absorption degradation rather than to the potent first pass metabolism. This assertion was further verified by a series of intervention studies, where improvement of lipid solubility and intestinal permeability as well as inhibition of intestinal flora increased the relative bioavailability to different extents without being changed by P-gp inhibition. After intravenous administration, the cumulative excretion rates of ASD in the urine and bile were 14.79 ± 1.87%, and 21.76 ± 17.61% respectively, but only 0.011% in feces, suggesting that the urine and bile were the main excretion pathways and that there was a large amount of biotransformation in the gastrointestinal tract. Fifteen possible metabolites were observed in the urine, feces and bile. The main metabolites were ASD deglycosylation, demethylation, dehydroxylation, decarbonylation, decarboxylation, hydroxylation, hydroxymethylation, hydroxyethylation and hydrolysis.Conclusion: The pharmacokinetics, bioavailability, metabolism and excretion of ASD in rats were systematically evaluated for the first time in this study. It has been confirmed that the ultra-low oral bioavailability is due to poor gastrointestinal permeability, extensive pre-absorption degradation and biotransformation. ASD after iv administration is not only excreted by the urine and bile, but possibly undergoes complex metabolic elimination.

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Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System

Planta Medica ◽

10.1055/a-1270-7606 ◽

2020 ◽

Author(s):

Patcharawalai Jaisamut ◽

Subhaphorn Wanna ◽

Surasak Limsuwan ◽

Sasitorn Chusri ◽

Kamonthip Wiwattanawongsa ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Oral Bioavailability ◽

Biological Activities ◽

Area Under The Curve ◽

Aqueous Solubility ◽

The Self

AbstractBoth quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

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HPLC-MS/MS-Mediated Analysis of the Pharmacokinetics, Bioavailability, and Tissue Distribution of Schisandrol B in Rats

International Journal of Analytical Chemistry ◽

10.1155/2021/8862291 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Dahu Liang ◽

Zijing Wu ◽

Yanhao Liu ◽

Chao Li ◽

Xianghong Li ◽

...

Keyword(s):

Tissue Distribution ◽

Oral Bioavailability ◽

Internal Standard ◽

Rat Plasma ◽

Absolute Bioavailability ◽

Sprague Dawley ◽

Linear Calibration ◽

Tissue Homogenates ◽

Distribution Studies

Schisandrol B, a lignan isolated from dried Schisandra chinensis fruits, has been shown to exhibit hepatoprotective, cardioprotective, renoprotective, and memory-enhancing properties. This study sought to design a sensitive and efficient HPLC-MS/MS approach to measuring Schisandrol B levels in rat plasma and tissues in order to assess the pharmacokinetics, oral bioavailability, and tissue distributions of this compound in vivo. For this analysis, bifendate was chosen as an internal standard (IS). A liquid-liquid extraction (LLE) approach was employed for the preparation of samples that were subsequently separated with an Agilent ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm) column with an isocratic mobile phase consisting of methanol and water containing 5 mM ammonium acetate and 0.1% formic acid (90 : 10, v/v). A linear calibration curve was obtained over the 5–2000 ng/mL and 1–1000 ng/mL ranges for plasma samples and tissue homogenates, respectively. This established method was then successfully applied to investigate the pharmacokinetics, oral bioavailability, and tissue distributions of Schisandrol B in Sprague-Dawley (SD) rats that were intravenously administered 2 mg/kg of Schisandrol B monomer, intragastrically administered Schisandrol B monomer (10 mg/kg), or intragastrically administered 6 mL/kg SCE (equivalent to 15 mg/kg Schisandrol B monomer). The oral absolute bioavailability of Schisandrol B following intragastric Schisandrol B monomer and SCE administration was approximately 18.73% and 68.12%, respectively. Tissue distribution studies revealed that Schisandrol B was distributed throughout several tested tissues, with particular accumulation in the liver and kidneys. Our data represent a valuable foundation for future studies of the pharmacologic and biological characteristics of Schisandrol B.

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Pharmacokinetic Evaluation of 3′-Azido-2′, 3′-Dideoxyuridine-5′-O-Valinate-Hydrochloride as a Prodrug of the Anti-HIV Nucleoside 3′-Azido-2′, 3′-Dideoxyuridine

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020301400505 ◽

2003 ◽

Vol 14 (5) ◽

pp. 263-270

Author(s):

Linghui Kong ◽

John S Cooperwood ◽

Shu-Hui Christine Huang ◽

Chung K Chu ◽

F Douglas Boudinot

Keyword(s):

Oral Administration ◽

Intravenous Administration ◽

Oral Bioavailability ◽

Half Life ◽

Dose Range ◽

Parent Compound ◽

Terminal Phase ◽

Pharmacokinetic Parameters ◽

Intravenous And Oral Administration ◽

Anti Hiv

3′-Azido-2′, 3′-dideoxyuridine (AZDU, AzddU, CS-87) has been shown to have potent anti-HIV activity in vitro. However, the compound exhibits a relatively short half-life and incomplete oral bioavailability in humans. In an effort to improve the pharmacokinetic properties of AZDU, prodrug 3′-azido-2′,3′-dideoxyuridine-5′- O-valinate hydrochloride (AZDU-VAL) was synthesized by the esterification of 5′-OH function in AZDU. The objective of this study was to investigate the biotransformation and pharmacokinetics of AZDU-VAL along with its antiviral parent compound AZDU following intravenous and oral administration to rats. Adult male Sprague-Dawley rats were administered AZDU or AZDU-VAL by intravenous injection or oral gavage. Concentrations of AZDU-VAL and AZDU were determined by HPLC. Pharmacokinetic parameters were generated by area-moment analysis. The bioavailability of AZDU after oral administration was approximately 53%. The terminal phase half-life of the nucleoside analogue ranged between 0.6 h after intravenous administration and 1 h following oral administration. In vivo the prodrug was rapidly and efficiently biotransformed to yield AZDU following intravenous and oral administration. The apparent availability of AZDU was virtually complete following oral administration of prodrug AZDU-VAL averaging 101%. The bioavailability of AZDU following intravenous administration of AZDU-VAL averaged 106%. In summary, the disposition of AZDU was dose dependent over the dose range of 25–100 mg/kg. Renal clearance and steady state volume of distribution were lower at the higher dose level. Prodrug AZDU-VAL demonstrated improved oral bioavailability as evidenced by complete absorption and efficient bioconversion to AZDU. The results suggest that AZDU-VAL may be a promising prodrug for the delivery of AZDU.

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Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

10.21203/rs.3.rs-286030/v1 ◽

2021 ◽

Author(s):

Zhuomin Xu ◽

Shanshan Zheng ◽

Yulu Hong ◽

Yue Cai ◽

Qiuqin Zhang ◽

...

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Biological Activities ◽

Low Cost ◽

Polarized Light ◽

Average Diameter ◽

Future Application ◽

Amorphous Solid Dispersion ◽

Self Assembled

Abstract Background: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy.Results: CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was -11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about 2 time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth.Conclusions: Na2GA/CA-BM nanoparticles (131.6 nm, -11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.

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Quantitative Determination of AZD3264, a Selective Ikb-Kinase IKK2 Inhibitor, in Dog Plasma by Solvent-Induced Phase Transition Extraction Coupled with HPLC-MS/MS and its Application to Pharmacokinetic Study in Dogs

Journal of AOAC International ◽

10.1093/jaoacint/qsaa134 ◽

2020 ◽

Author(s):

Gang Li ◽

Shuofu Liang ◽

Kesen Qiao ◽

Chao Wang

Keyword(s):

Phase Transition ◽

Intravenous Administration ◽

Internal Standard ◽

Selected Reaction Monitoring ◽

Pharmacokinetic Studies ◽

Preclinical Development ◽

Bioanalytical Method Validation ◽

Dog Plasma ◽

Carry Over

Abstract Background AZD3264 is a small molecule inhibitor of selective IkB-kinase IKK2 currently in preclinical development for the potential treatment of asthma and chronic pulmonary obstructive disorder. Objective A method for the quantitative analysis of AZD3264 was established and optimized by using HPLC tandem mass spectrometry in dog plasma. Method Plasma samples were pretreated using a solvent-induced phase transition extraction method with a methanol solution of omeprazole as the internal standard. Chromatographic separation was performed using a Thermo Hypersil GOLD-C18 (50 mm × 4.6 mm, 3 μm) column with the temperature maintained at 25°C. Mobile phase consisted of 0.1% formic acid in water and acetonitrile in a gradient mode at a flow rate of 0.6 mL/min. Mass spectrometric detection was carried out in selected reaction monitoring mode with positive electrospray ionization, and the mass transitions of AZD3264 and omeprazole were m/z 442.1 → 425.0 and m/z 346.0 → 198.0, respectively. Results The intra-batch accuracy was within 95.11–105.06% and the precision was within 6.50–9.98%. The inter-batch accuracy was within 96.83–102.80% with a precision of 7.62–9.50%. The selectivity, sensitivity, linearity, dilution linearity, extraction recovery and matrix effect, stability, and carry-over met all requirements of the guidelines for bioanalytical method validation. AZD3264 showed linear pharmacokinetic characteristics following intravenous administration to dogs at 0.3–2.7 mg/kg. Conclusions The developed and validated method was successfully employed in pharmacokinetic studies in dogs following intravenous administration at the doses of 0.3, 0.9, and 2.7 mg/kg. Highlights This was the first investigation of the in vivo pharmacokinetic characteristics of AZD3264 in dogs by LC-MS/MS with SIPTE method for plasma sample preparation.

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Pharmacokinetic and Bioavailability Studies of Embelin after Intravenous and Oral Administration to Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9682495 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Zhen Li ◽

Shu-jing Chen ◽

Xie-an Yu ◽

Jin Li ◽

Xiu-mei Gao ◽

...

Keyword(s):

Phosphoric Acid ◽

Oral Bioavailability ◽

High Performance ◽

Internal Standard ◽

Rat Plasma ◽

Hepatoprotective Activity ◽

Array Detector ◽

Limit Of Quantification ◽

Intravenous And Oral Administration

Embelin exhibits the broad bioactivities such as antitumor, antifertility, antidiabetic, anti-inflammatory, antioxidant, anticonvulsant, anxiolytic, antimicrobial, and hepatoprotective activity. In order to further understand the pharmacokinetic characteristics and oral bioavailability of embelin in vivo, the concentration of embelin in rat plasma was determined by a sensitive high-performance liquid chromatography with diode array detector (HPLC-DAD). The preparation of samples was accomplished by a simple precipitating protein with methanol. Emodin was selected as the internal standard (IS). Embelin and IS were completely separated on an analytical column (Extend-C18, 4.6 × 250 mm, 5 μm) using 0.1% phosphoric acid in methanol and 0.1% phosphoric acid in aqueous solution (90:10, v/v) as the mobile phase. The lower limit of quantification was 0.15 μg/mL. Oral bioavailability of embelin was 30.2 ± 11.9%. This study could provide the information about pharmacokinetics and oral bioavailability of embelin, which was useful to assess the clinic efficacy and safety and promote further development of embelin.

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Pharmacokinetics and Tissue Distribution of Alnustone in Rats after Intravenous Administration by Liquid Chromatography-Mass Spectrometry

Molecules ◽

10.3390/molecules24173183 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3183 ◽

Cited By ~ 2

Author(s):

Yang Song ◽

Yu Zhou ◽

Xiao-Ting Yan ◽

Jing-Bo Bi ◽

Xin Qiu ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Formic Acid ◽

Tissue Distribution ◽

Intravenous Administration ◽

Peak Plasma ◽

Internal Standard ◽

Pharmacokinetic Studies ◽

The Mean

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between −8.2–9.7% and −10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL∙h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

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Pharmacokinetics of 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)uracil in woodchucks.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.10.2184 ◽

1997 ◽

Vol 41 (10) ◽

pp. 2184-2187 ◽

Cited By ~ 19

Author(s):

J W Witcher ◽

F D Boudinot ◽

B H Baldwin ◽

M A Ascenzi ◽

B C Tennant ◽

...

Keyword(s):

Animal Model ◽

Oral Administration ◽

Intravenous Administration ◽

High Performance ◽

Hepatitis Virus ◽

Volume Of Distribution ◽

Terminal Phase ◽

Intravenous And Oral Administration

1-(2-Fluoro-5-methyl-beta-L-arabinofuranosyl)uracil (L-FMAU) is a nucleoside analog with potent in vitro activity against hepatitis B virus (HBV) and Epstein-Barr virus. The purpose of this study was to characterize the disposition of L-FMAU following oral and intravenous administration in the woodchuck animal model. The numerous similarities between woodchuck hepatitis virus and HBV infection justify the use of the woodchuck as an animal model for preclinical studies of anti-HBV agents in vivo. Woodchucks were given 25 mg of L-FMAU per kg of body weight intravenously and orally. Concentrations of L-FMAU in urine and plasma were determined by high-performance liquid chromatography. Following intravenous administration of 25 mg of L-FMAU per kg to woodchucks, total clearance was moderate, averaging 0.23 +/- 0.07 liter/h/kg. Renal clearance and nonrenal clearance averaged 0.13 +/- 0.08 and 0.10 +/- 0.06 liter/h/kg, respectively. The steady-state volume of distribution averaged 0.99 +/- 0.17 liter/kg, indicative of intracellular distribution of the nucleoside. The terminal-phase half-life of L-FMAU following intravenous administration averaged 6.2 +/- 2.0 h, and mean residence time averaged 4.5 +/- 0.8 h. Absorption of L-FMAU after oral administration was incomplete, and bioavailability was approximately 20%. Concentrations of L-FMAU in plasma remained above the in vitro 50% effective concentration of 0.026 microg/ml for HBV (C. K. Chu, T. Ma, K. Shanmuganathan, C. Wang, Y. Xiang, S. B. Pai, G.-Q. Yao, J.-P. Sommadossi, and Y.-C. Cheng, Antimicrob. Agents Chemother. 39:979-981, 1995) for 24 h after both intravenous and oral administration of 25 mg of L-FMAU per kg.

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Pharmacokinetics of a water-soluble fullerene in rats.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.10.2262 ◽

1996 ◽

Vol 40 (10) ◽

pp. 2262-2265 ◽

Cited By ~ 73

Author(s):

P Rajagopalan ◽

F Wudl ◽

R F Schinazi ◽

F D Boudinot

Keyword(s):

Human Immunodeficiency Virus ◽

Intravenous Administration ◽

Biological Activities ◽

Intraperitoneal Administration ◽

Water Soluble ◽

Fullerene Derivative ◽

Terminal Phase ◽

Binding Studies ◽

Analytical Methodology ◽

Immunodeficiency Virus

Fullerenes are the recently discovered third allotropic form of carbon. The biological activities of these compounds are being studied for various purposes. The bis(monosuccinimide) derivative of p p'-bis(2-amino-ethyl)-diphenyl-C60 (MSAD-C60) is a water-soluble fullerene derivative. MSAD-C60 has been shown to have antiviral activity against human immunodeficiency virus types 1 and 2 in vitro and to have virucidal and anti-human immunodeficiency virus protease activities. Moreover, MSAD-C60 has been shown to be well tolerated in mice after intraperitoneal administration. The purpose of the present study was to develop a high-performance liquid chromatographic analytical methodology for MSAD-C60 and to characterize the preclinical pharmacokinetics of the compound in rats. Following intravenous administration of the fullerene derivative at a dose of 15 mg/kg of body weight, the concentrations of MSAD-C60 in plasma declined either bi- or triexponentially. The mean terminal-phase half-life of MSAD-C60 was 6.8 +/- 1.1 h (mean +/- standard deviation). Binding studies indicated that the compound is greater than 99% bound to plasma proteins. The average total clearance of the compound was 0.19 +/- 0.06 liter/h/kg. Urine samples obtained 24 h after intravenous administration did not contain detectable levels of the compound, indicating the absence of a significant renal clearance mechanism. The steady-state volume of distribution of MSAD-C60 averaged 2.1 +/- 0.8 liters/kg, indicating that the compound distributes into tissues. At a dose of 15 mg/kg, MSAD-C60 appeared to be well tolerated. However, a dose of 25 mg/kg resulted in shortness of breath and violent movement of the rats, followed by death within 5 min of dosing. Further controlled toxicity studies are needed to fully evaluate the toxicity of the compound.

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Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00911-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Zhuomin Xu ◽

Shanshan Zheng ◽

Xin Gao ◽

Yulu Hong ◽

Yue Cai ◽

...

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Biological Activities ◽

Low Cost ◽

Polarized Light ◽

Average Diameter ◽

Future Application ◽

Amorphous Solid Dispersion ◽

Self Assembled

Abstract Background Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy. Results CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was − 11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about two time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth. Conclusions Na2GA/CA-BM nanoparticles (131.6 nm, − 11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment. Graphic abstract

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