Preparation and evaluation of dissolving tofacitinib microneedles for effective management of rheumatoid arthritis.

Dissolving microneedles have become a focal point in transdermal drug delivery. They have the advantages of painless, rapid drug delivery and high drug utilization. The purpose of this study was to evaluate the efficacy of Tofacitinib citrate microneedles in arthritis treatment, assess the dose-effect relationship, and determine the cumulative penetration during percutaneous injection. In this study, block copolymer was utilized to prepare the dissolving microneedles. The microneedles were characterized through skin permeation tests, dissolution tests, treatment effect evaluations, and Western blot experiments. In vivo dissolution experiments revealed that the soluble microneedles completely dissolved within 2.5 min, while in vitro skin permeation experiments demonstrated the highest unit area of skin permeation of the microneedles reached 2118.13 mg/cm2. The inhibition of Tofacitinib microneedle on joint swelling in rats with Rheumatoid arthritis was better than Ketoprofen and close to that of oral Tofacitinib. Western-blot experiment comfirmed the Tofacitinib microneedle's inhibitory effect on the JAK-STAT3 pathway in rats with Rheumatoid arthritis. In conclusion, Tofacitinib microneedles effectively inhibited arthritis in rats, demonstrating potential for Rheumatoid arthritis treatment.

A transfersomes hydrogel patch for cutaneous delivery of propranolol hydrochloride: formulation, in vitro, ex vivo and in vivo studies.

OBJECTIVE: In this work, a propranolol hydrochloride (PRH) transfersomes loaded cutaneous hydrogel patch was developed for topical drug delivery in the affected area of infantile haemangioma. METHODS: Sodium cholate was used as the edge activator to prepare the transfersomes. Based on the central composite design, transfersomes hydrogel patch formulation was optimised with 48 h cumulative penetration and time lag as response values. Particle sizes and morphology of the prepared transfersomes were assessed. They were loaded in a cutaneous hydrogel patch, after which their skin permeation abilities were evaluated, and histopathological effects were investigated using guinea pigs. Moreover, in vivo pharmacokinetics studies were performed in rats. RESULTS: The transfersomes system had a encapsulation efficiency of 81.84 ± 0.53%, particle size of 186.8 ± 3.38 nm, polydispersity index of 0.186 ± 0.002, and a zeta potential of -28.6 ± 2.39 mV. Transmission electron microscopy images revealed sphericity of the particles. The ex vivo drug's penetration of the optimised transfersomes hydrogel patch was 111.05 ± 11.97 µg/cm2 through rat skin within 48 h. Assessment of skin tissue did not reveal any histopathological alterations in epidermal and dermal cells. Pharmacokinetic studies showed that skin Cmax (68.22 µg/cm2) and AUC0-24 (1007.33 µg/cm2 × h) for PRH transfersomes hydrogel patch were significantly higher than those of commercially available oral dosage form and hydrogel patch without transfersomes. These findings imply that the transfersomes hydrogel patch can prolong drug accumulation in the affected skin area, and reduce systemic drug distribution via the blood stream. CONCLUSIONS: The hydrogel patch-loaded PRH transfersomes is a potentially useful drug formulation for infantile haemangioma.

Transdermal iontophoresis delivery system for terazosin hydrochloride: an in vitro and in vivo study.

This study aimed to construct a transdermal iontophoresis delivery system for terazosin hydrochloride (IDDS-TEH), which included a positive and negative electrode hydrogel prescription. Intact guinea pig skin was used as a model for the skin barrier function, and the current intensity, terazosin hydrochloride (TEH) concentration, pH, competitive salt, and transdermal enhancer properties were studied. The blood drug concentration was determined in Sprague-Dawley (SD) rats using HPLC, and the antihypertensive effects of IDDS-TEH were evaluated in spontaneously hypertensive rats (SHRs). The results showed that the steady-state penetration rate of TEH increased (from 80.36 µg·cm-2·h-1 to 304.93 µg·cm-2·h-1), followed by an increase in the current intensity (from 0.10 mA·cm-2 to 0.49 mA·cm-2). The pH values also had a significant influence on percutaneous penetration. The blood concentration of IDDS-TEH was significantly higher (p < .05) than with passive diffusion, which could not be detected. The main pharmacokinetic parameters of the high current group (0.17 mA·cm-2) and the low current group (0.09 mA·cm-2) were AUC0-t: 5873.0 ng·mL-1·h and 2493.7 ng·mL-1·h, respectively. Meanwhile, the pharmacodynamic results showed that IDDS-TEH significantly decreased the blood pressure of SHRs compared with the TEH hydrogel without loading current. Therefore, TEH could be successfully delivered by the transdermal iontophoresis system in vitro and in vivo, and further clinical studies should be explored to develop a therapeutically useful protocol.