Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.
Humans ; Drug Delivery Systems ; Administration, Cutaneous ; Pharmaceutical Preparations ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Needles

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.
Administration, Cutaneous ; Skin Absorption ; Chromatography, Liquid ; Oils, Volatile ; Viscosity

This study aims to establish a rapid and sensitive UPLC-MS/MS method for simultaneously determining the content of strychnine and paeoniflorin in plasma and brain tissue of rats, and compare the pharmacokinetic behavior and brain tissue distribution of paeoniflorin combined with normal and toxic doses of strychnine in rats after percutaneous administration. Compared with those in the toxic-dose strychnine group, the AUC_(0-t), AUC_(0-∞), and C_(max) of strychnine decreased by 51.51%, 45.68%, and 46.03%, respectively(P<0.01), and the corresponding values of paeoniflorin increased by 91.41%, 102.31%, and 169.32%, respectively(P<0.01), in the compatibility group. Compared with the normal-dose strychnine group, the compatibility group showed insignificantly decreased C_(max), AUC_(0-t), and AUC_(0-∞) of strychnine, increased C_(max) and T_(max) of paeoniflorin(P<0.01), 66.88% increase in AUC_(0-t), and 70.55% increase in AUC_(0-∞) of paeoniflorin. In addition, the brain tissue concentration of strychnine decreased and that of paeoniflorin increased after compatibility. The combination of paeoniflorin with normal dose and toxic dose of strychnine can inhibit the percutaneous absorption of strychnine, and greatly promote the percutaneous penetration of paeoniflorin, whereas the interaction mechanism remains to be explored. The UPLC-MS/MS method established in this study is easy to operate and has good precision. It is suitable for in vivo study of pharmacokinetic behavior and brain tissue distribution of paeoniflorin and strychnine after percutaneous administration in rats, which provides reference for the safe and rational clinical use of strychnine and the combined use of drugs, and lays a solid foundation for the development of external preparations containing Strychni Semen.
Administration, Cutaneous ; Animals ; Brain ; Bridged-Ring Compounds/pharmacology* ; Chromatography, Liquid/methods* ; Glucosides ; Monoterpenes ; Rats ; Rats, Sprague-Dawley ; Strychnine ; Tandem Mass Spectrometry/methods* ; Tissue Distribution

Essential oils(EOs) from Chinese medicinals, which can be used as adjuvants and exert certain therapeutic effect, are directly used in Chinese medicine formulas. Conventional research strategy for EOs from Chinese medicinals is to compare the efficacy of the prescriptions before and after the addition of EOs, and the penetration-enhancing mechanisms of EOs remain unclear. In modern research on EOs from Chinese medicinals, the method for studying chemical penetration enhancers is often used, which fails to reflect the overall efficacy of EOs. This study clarified the property regularity of EOs from Chinese medicinals as transdermal penetration enhancers, and thereby proposed a research model which integrated the medicinal and adjuvant properties of EOs from Chinese medicinals via "component-delivery-effect" characterization route. The core concept is that constituents of EOs from Chinese medicinals and their delivery process play a key role in their external application. This research model is expected to serve as a reference for further research on EOs from Chinese medicinals for transdermal application.
Adjuvants, Pharmaceutic ; Administration, Cutaneous ; China ; Drugs, Chinese Herbal/pharmacology* ; Oils, Volatile/pharmacology*

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.
Administration, Cutaneous ; Chromatography, Liquid ; Emulsions ; Permeability ; Skin/metabolism* ; Skin Absorption ; Tandem Mass Spectrometry

Objective: To explore the clinical features and treatment of pyoderma gangrenosum (PG). Methods: A retrospective observational study was conducted. From January 2012 to July 2021, 25 patients with PG who met the inclusion criteria were admitted to Beijing Fucheng Hospital, including 16 males and 9 females, with the age of onset of disease being 14 to 75 years. Among them, the classification of PG identified 17 cases of ulcerative type, 6 cases of pustular type, 1 case of proliferative type, and 1 case of bullous type. Six patients were accompanied with systemic diseases, while 19 patients were not accompanied with systemic diseases. At the same time of systemic treatment with glucocorticoids, dressing changes or surgical skin grafting was performed on the wounds. The results of laboratory and histopathological examinations, the overall curative effects and follow-up of patients, the wound healing time of patients with negative and positive microbial culture results of wound secretion specimens, and the curative effects of patients with and without systemic diseases were analyzed. Results: The results of blood routine examination of 19 patients were abnormal, and all the immunological indexes were normal in all the patients; the microbial culture results of wound secretion specimens were positive in 14 patients; and the histopathological examination results of ulcer boundary tissue in 15 patients with rapid wound progress were mainly local tissue inflammatory changes. The wounds were cured in 17 patients, mostly healed in 7 patients, and not healed in 1 patient. After one-year's follow-up, the PG in 3 patients relapsed due to self-discontinuation of medication after discharge, and the wounds were healed gradually after adjustment of medication, while the remaining patients had no relapse. The days of wound healing in 14 patients with positive microbial culture results of wound secretion specimens were 21-55 days, and the days of wound healing in 11 patients with negative microbial culture results in wound secretion specimens were 20-54 days. In the 6 patients with systemic diseases, the wounds of 3 patients were cured, and the wounds of the other 3 patients were mostly healed. In the 19 patients without systemic diseases, the wounds of 14 patients were cured, the wounds of 4 patients were mostly healed, and the wound of 1 patient was not healed. Conclusions: The laboratory examination and pathological manifestations of patients with PG lacks characteristics, and their clinical manifestations are rich and diverse, thus PG can be easily misdiagnosed. The glucocorticoids combined with immunosuppressive therapy have good effects on PG. Surgical intervention can be performed on the wounds. Specifically, excessive debridement is not recommended in the acute phase, but skin grafting can be performed in the contraction phase.
Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Female ; Glucocorticoids ; Humans ; Male ; Middle Aged ; Pyoderma Gangrenosum/therapy* ; Skin Transplantation ; Wound Healing ; Young Adult

OBJECTIVE: To compare the clinical efficacy between auricular point sticking combined with transcutaneous electrical acupoint stimulation (TEAS) and nicotine patch for smoking cessation. METHODS: Two hundred patients who voluntarily quit smoking were randomly divided into a combination group and a nicotine patch group, 100 cases in each group. In the combination group, auricular point sticking (Shenmen [TF₄], Neifenmi [CO₁₈], Pizhixia [AT₄], Jiaogan [AH_6a], etc., once every other day) combined with TEAS（Lieque [LU 7] and Zusanli [ST 36], with continuous wave, 20 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day) were applied. In the nicotine patch group, nicotine patch was applied. Both groups were treated for 8 weeks. The immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and in follow-up of 16 weeks after treatment in the two groups were compared; before treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the degree of nicotine dependence was evaluated by using Fagerström test for nicotine dependence (FTND); 1 week into treatment, 8 weeks into treatment and in follow-up of 16 weeks after treatment, the withdrawal symptoms and smoking craving were evaluated by using Minnesota nicotine withdrawal scale (MNWS); the safety and compliance (dropped off rate and treatment completeness) were evaluated in the two groups. RESULTS: There was no statistical significance of the differences in the immediate withdrawal rate and persistent withdrawal rate 8 weeks into treatment and during follow-up between the two groups (P>0.05). The FTND scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those before treatment (P<0.01); the FTND score during follow-up in the combination group was lower than the nicotine patch group (P<0.05). The MNWS scores were decreased 8 weeks into treatment and during follow-up in the two groups compared with those 1 week into treatment (P<0.05); the changes of MNWS scores 8 weeks into treatment and during follow-up in the combination group were greater than the nicotine patch group (P<0.05, P<0.01). There were no serious adverse reactions in either group. Eight weeks into treatment and during follow-up, the dropped off rates were all 16.0% (16/100) in the combination group, which were 20.0% (20/100) and 23.0% (23/100) in the nicotine patch group, there was no statistical significance of the differences in the two groups (P>0.05). There was no significant difference in treatment completeness between the two groups (P>0.05). CONCLUSION Auricular point sticking combined with TEAS could effective decrease the degree of nicotine dependence, improve withdrawal symptoms in smokers, its effect is superior to nicotine patch.
Humans ; Smoking Cessation ; Tobacco Use Disorder ; Acupuncture Points ; Administration, Cutaneous ; Nicotine ; Substance Withdrawal Syndrome/drug therapy*

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

Microneedles have been developed rapidly in the field of transdermal administration in the past few decades. In recent years, the development of microelectronics technology has expanded the applications of microneedles by combining with microelectronic systems, especially in biological diagnosis and treatment. Different types of microneedles have been designed to extract blood and tissue fluids for detection, or as electrodes to directly detect blood sugar, melanoma and pH in real-time in vivo, both show good prospects for real-time detection applications. In this paper, we review the design of materials and structure of microelectronic-based microneedles, and discuss their advances in biological diagnosis.
Administration, Cutaneous ; Drug Delivery Systems ; Electrodes ; Microinjections ; Needles

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.
Administration, Cutaneous ; Diterpenes ; Drug Delivery Systems ; Epoxy Compounds ; Needles ; Phenanthrenes ; Skin