The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Background: Tong-Bi-Si-Wei-Fang (TBSWF) is a candidate formula of Traditional Chinese Medicine (TCM) for treating rheumatoid bone diseases, which is composed of rhizoma corydalis alkaloids, saponins of glycyrrhiza uralensis and panax notoginseng, flavonoids of rhizoma drynariae and glycyrrhiza uralensis. </P><P> Objective: Trahydropalmatine (THP), the main active ingredient of rhizoma corydalis alkaloids, was selected to study in vivo pharmacokinetics and druggability of TBSWF. Methods: The plasma concentration-time (C-T) profiles of THP and the pharmacokinetic property parameters after oral administration of THP monomer, extract of corydalis alkaloids (ECA) and TBSWF to rats, respectively were compared by a fully-validated HPLC method. Results: Compared to the THP monomer, the THP in TBSWF is absorbed faster, resides in the plasma longer and has a similar apparent volume of distribution Vz/F (10~20 L/kg). Compared to THP monomer and THP in TBSWF, the area under the concentration-time curve AUC 0-t of THP in ECA decreases two-third; Vz/F of THP in ECA (85.02 L/kg) is significantly higher than that of THP in TBSWF(p <0.05). Unlike THP monomer and THP in ECA, double peaks are observed in the C-T profile of THP after oral administration of TBSWF. THP in TBSWF exhibits slow release to a certain degree. Conclusion: The interactions among the ingredients of TBSWF promote the adsorption and prolong the residence time of THP in vivo, and provide an explanation for the advantages of TBSWF from the point of pharmacokinetics.

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Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections

Nano Letters ◽

10.1021/acs.nanolett.0c04578 ◽

2021 ◽

Vol 21 (2) ◽

pp. 1124-1131

Author(s):

Le Wang ◽

Junchuan Yang ◽

Sixiang Li ◽

Qizhen Li ◽

Shaoqin Liu ◽

...

Keyword(s):

Gold Nanoparticles ◽

Oral Administration ◽

In Vivo Synthesis

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In-vitro and in-vivo metabolism of different aspirin formulations studied by a validated liquid chromatography tandem mass spectrometry method

Scientific Reports ◽

10.1038/s41598-021-89671-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michele Dei Cas ◽

Jessica Rizzo ◽

Mariangela Scavone ◽

Eti Femia ◽

Gian Marco Podda ◽

...

Keyword(s):

Oral Administration ◽

Whole Blood ◽

Serum Levels ◽

Reversed Phase ◽

Weekly Treatment ◽

Low Dose Aspirin ◽

Liquid Chromatography Tandem Mass ◽

Enteric Coated

AbstractLow-dose aspirin (ASA) is used to prevent cardiovascular events. The most commonly used formulation is enteric-coated ASA (EC-ASA) that may be absorbed more slowly and less efficiently in some patients. To uncover these “non-responders” patients, the availability of proper analytical methods is pivotal in order to study the pharmacodynamics, the pharmacokinetics and the metabolic fate of ASA. We validated a high-throughput, isocratic reversed-phase, negative MRM, LC–MS/MS method useful for measuring circulating ASA and salicylic acid (SA) in blood and plasma. ASA-d4 and SA-d4 were used as internal standards. The method was applied to evaluate: (a) the "in vitro" ASA degradation by esterases in whole blood and plasma, as a function of time and concentration; (b) the "in vivo" kinetics of ASA and SA after 7 days of oral administration of EC-ASA or plain-ASA (100 mg) in healthy volunteers (three men and three women, 37–63 years). Parameters of esterases activity were Vmax 6.5 ± 1.9 and Km 147.5 ± 64.4 in plasma, and Vmax 108.1 ± 20.8 and Km 803.2 ± 170.7 in whole blood. After oral administration of the two formulations, tmax varied between 3 and 6 h for EC-ASA and between 0.5 and 1.0 h for plain-ASA. Higher between-subjects variability was seen after EC-ASA, and one subject had a delayed absorption over eight hours. Plasma AUC was 725.5 (89.8–1222) for EC-ASA, and 823.1(624–1196) ng h/mL (median, 25–75% CI) for plain ASA. After the weekly treatment, serum levels of TxB2 were very low (< 10 ng/mL at 24 h from the drug intake) in all the studied subjects, regardless of the formulation or the tmax. This method proved to be suitable for studies on aspirin responsiveness.

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Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽

10.1177/1559325820987943 ◽

2021 ◽

Vol 19 (1) ◽

pp. 155932582098794

Author(s):

Imran Mukhtar ◽

Haseeb Anwar ◽

Osman Asghar Mirza ◽

Qasim Ali ◽

Muhammad Umar Ijaz ◽

...

Keyword(s):

Oral Administration ◽

Gut Microbiome ◽

Drug Target ◽

Membrane Transporters ◽

Intestinal Microbiome ◽

Albino Rats ◽

Body Organ ◽

Total Absorbance ◽

Research World

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

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Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein

Clinical and Developmental Immunology ◽

10.1155/2011/831704 ◽

2011 ◽

Vol 2011 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Qiaohong Meng ◽

Wenfeng Wang ◽

Xiaowen Shi ◽

Yongfeng Jin ◽

Yaozhou Zhang

Keyword(s):

Fusion Protein ◽

Oral Administration ◽

Fluorescent Protein ◽

Autoimmune Diabetes ◽

Nod Mice ◽

Treg Cells ◽

Immunological Tolerance ◽

Protein Vaccine ◽

Green Fluorescent

In animals, oral administration of the cholera toxin B (CTB) subunit conjugated to the autoantigen insulin enhances the specific immune-unresponsive state. This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1Din vivoremains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4+CD25+Foxp3+T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4+CD25+Foxp3+Treg cells in treating T1D.

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Alterations in metabolism of cytidine components in rat liver after oral administration of butylated hydroxytoluene (in vivo study)

Toxicology ◽

10.1016/0300-483x(79)90062-3 ◽

1979 ◽

Vol 14 (2) ◽

pp. 167-178 ◽

Cited By ~ 2

Author(s):

J. Seifert ◽

E. Buchar

Keyword(s):

Oral Administration ◽

Rat Liver ◽

Butylated Hydroxytoluene ◽

In Vivo Study

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Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats

Human & Experimental Toxicology ◽

10.1177/096032719701600410 ◽

1997 ◽

Vol 16 (4) ◽

pp. 212-216 ◽

Cited By ~ 13

Author(s):

Alison F Lailey

Keyword(s):

Oral Administration ◽

Pulmonary Oedema ◽

Plasma Levels ◽

Pyrolysis Product ◽

Lavage Fluid ◽

Lethal Effects ◽

Duration Of Protection ◽

Gas Exposure

1 Perfluoroisobutene, a pyrolysis product of polytetra fluoroethene may cause pulmonary oedema and death when inhaled. Oral N-acetylcysteine has shown protection against inhalation of perfluoroisobutene and in this study we have tried to elucidate the mechanism by which protection is mediated. 2 Protection against the lethal effects of inhaled per fluoroisobutene has been shown when N-acetylcys teine has been orally administered 4, 6 or 8 h before gas exposure. 3 Plasma levels of cysteine, glutathione and N-acetylcys teine were increased for up to 7 h following oral administration of Nac. 4 N-acetylcysteine was not detected in the bronchio alveolar lavage fluid following oral administration. 5 Duration of protection in vivo has been related to the duration of increased thiol levels in the plasma.

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Attribution and identification of absorbed components by HPLC-DAD-ESI-MS after oral administration of Erhuang decoction

Journal of Analytical Science & Technology ◽

10.1186/s40543-020-00236-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Jinglong Wang ◽

Dandan Zheng ◽

Nan Xu ◽

Chao Zhang ◽

Yingzi Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Oral Administration ◽

Mass Spectrometry Data ◽

Mass Spectrometry Analysis ◽

Original Form ◽

Bioactive Constituents ◽

Serum Samples ◽

Rat Serum ◽

Esi Ms

AbstractTo realize the attribution and identification of absorbed components in rat serum after oral administration of Erhuang decoction prepared by semi-bionic enzyme extraction method, the fingerprints of serum samples were established using a HPLC-DAD-ESI-MS method. Thirty-two peaks in Erhuang decoction and 24 peaks in rat serum after oral administration of Erhuang decoction were detected. Among the 24 peaks detected in rat serum, 25 compounds were identified by comparing the retention time and mass spectrometry data with that of reference compounds, or by mass spectrometry analysis and retrieving the reference literatures. Among the identified 25 compounds in vivo, 24 were the original form of compounds absorbed from the detected compounds in vitro, and one was the metabolite compounds of licorice. By analyzing the mass spectrometry or ultraviolet absorption characteristics, other unidentified compounds in vivo were deduced to be the endogenous metabolites in serum or the original form and metabolites of the compounds existed in vivo. Results indicated that HPLC-DAD-ESI-MS is suitable for identifying the bioactive constituents in serum after oral administration of Erhuang decoction, and the findings would be beneficial to further research and development of the pharmacodynamic substance base of Erhuang decoction.

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