Construction of a Nano-Controlled Release Methotrexate Delivery System for the Treatment of Rheumatoid Arthritis by Local Percutaneous Administration

A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO2@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO2@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO2@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse’s toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO2@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO2@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy.

Pharmacokinetics and Tissue Distribution of Combined Triptolide and Paeoniflorin Regimen for Percutaneous Administration in Rats Assessed by Liquid Chromatography-Tandem Mass Spectrometry

Triptolide (TP) has shown potential in rheumatoid arthritis (RA) treatment, but the narrow therapeutic window limits its clinical application. In clinical practice, the compatibility of Tripterygium wilfordii and Paeonia lactiflora is often used to attenuate the toxicity of TP, but its compatibility mechanism has not been fully elucidated. The aim of this study was to investigate the pharmacokinetics and tissue distribution of a combined regimen of TP and paeoniflorin (PF) after transdermal administration in male and female Sprague Dawley (SD) rats via a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that after percutaneous administration of TP and PF, there was no significant difference in AUC (0-t) (area under the curve) of TP, the peak concentration decreased by 58.17%, and the peak time was delayed. The AUC (0-t) of PF increased significantly ( P < 0.01), the peak-reaching concentration and AUC (0-∞) increased, and the half-life and average retention time were shortened, indicating that TP absorption in rats may be delayed. After percutaneous administration of TP and PF, the content of TP in the heart, liver, spleen, lungs, and kidneys of male rats significantly decreased at 2 h ( P < 0.05) and the drug concentration in the liver tissues significantly decreased at 2 h, 4 h, and 8 h ( P < 0.05). The TP content in the spleen of female rats significantly decreased at 2 h and 4 h ( P < 0.05) and also decreased in other tissues, but not significantly. After percutaneous administration of TP and PF, the PF content in the heart, liver, spleen, lungs, and kidneys of male and female rats had no significant difference. However, after percutaneous administration of TP and PF, the TP concentration in the skin increased, suggesting that the amount of TP retained in the skin increased, thereby reducing its content in blood and tissues, producing a reduction in toxicity effect.

Bioanalytical Method Development and Validation of Veratraldehyde and Its Metabolite Veratric Acid in Rat Plasma: An Application for a Pharmacokinetic Study

A simple, sensitive, and rapid UHPLC-MS/MS method was developed for the simultaneous determination of veratraldehyde and its metabolite veratric acid in rat plasma. Cinnamaldehyde was used as an internal standard (IS) and the one-step protein precipitation method with 0.2% formic acid in acetonitrile (mobile phase B) was used for the sample extraction. Reversed C18 column (YMC-Triart C18 column, 50 mm × 2.0 mm, 1.9 µm) was used for chromatographic separation and was maintained at 30 °C. The total run time was 4.5 min and the electrospray ionization in positive mode was used with the transition m/z 167.07 → 139.00 for veratraldehyde, m/z 183.07 → 139.00 for veratric acid, and m/z 133.00 → 55.00 for IS. The developed method exhibited good linearity (r2 ≥ 0.9977), and the lower limits of quantification ranged from 3 to 10 ng/mL for the two analytes. Intra-day precision and accuracy parameters met the criteria (within ±15%) during the validation. The bioanalytical method was applied for the determination of veratraldehyde and veratric acid in rat plasma after oral and percutaneous administration of 300 and 600 mg/kg veratraldehyde. Using the analytical methods established in this study, we can confirm the absorption and metabolism of veratraldehyde in rats for various routes.

Application of physical factors in complex treatment of puerperas with postpartum endometritis

This study aimed to investigate the effectiveness of the complex therapy of postpartum endometritis (PE) using percutaneous electrophoresis of metronidazole in the main group of puerperas (n = 43, mean age 27.6 ± 5.2 years). Patients from the comparison group (n = 42, mean age 26.3 ± 4.1 years) received only basic treatment according to the protocol. This study determined the severity of the main symptoms of PE in puerperas before and after the treatment using the clinical scale. The effectiveness of the treatment was evaluated quantitatively. Electrophoretic percutaneous administration of metronidazole combined with basic drug therapy exerted a pronounced anti-inflammatory effect at the local and systemic levels and reduced the risk of infection in endometritis. Compared with the basic therapy of PE, the high therapeutic effectiveness of electrophoresis with metronidazole was established.

Efficacy and safety of percutaneous administration of dihydrotestosterone in children of different genetic backgrounds with micropenis

Background:Exogenous androgen supplement is an optional treatment for micropenis; however, its use in childhood is controversial due to potential side effects.Methods:Twenty-three children (mean age: 4.07±3.4 years) with micropenis of unknown causes harboring the 46,XY karyotype were recruited in an open prospective study. Androgen receptor (Results:Two patients were found withConclusions:Short term and local application of DHT at low doses in patients with micropenis could accelerate penile growth effectively without evident side effects; however, precautions still need be taken due to the paucity of long term study and the lack of ideal DHT dosage.