Recent trends, challenges and future outlook of transdermal drug delivery systems for rheumatoid arthritis therapy.

Brucine, a weak alkaline indole alkaloid, is one of the main bioactive and toxic constituents of Nux-vomica. Modern pharmacology studies and clinical practice demonstrate that brucine possesses wide pharmacological activities, such as anti-tumor, anti-inflammatory, analgesic, and the effects on cardiovascular system and nervous system, etc. However, its central nervous system toxicity severely limits its clinical application. Herein, the physicochemical properties, pharmacological activities, and toxicity of brucine were reviewed, and the novel strategies to address the toxicity issues were discussed, aiming to bring new insights into further research and application of this active component.

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Brucine: A Review of Phytochemistry, Pharmacology, and Toxicology.

Polymeric microneedle-mediated transdermal delivery of melittin for rheumatoid arthritis treatment

A novel double layer pipette tip magnetic dispersive solid phase extraction (DPT-MSPE) based on polyamidoamine-functionalized magnetic carbon nanotubes (PAMAM@Mag-CNTs) was developed for the purification of fifteen toxic alkaloids in meat dishes and vegetable dishes. PAMAM@Mag-CNTs were synthesized through direct reaction between the carboxy group on the surface of the Mag-CNTs and the peripheral amino group of the polyamidoamine (PAMAM) dendrimers. The magnetism of PAMAM@Mag-CNTs simplified the post-processing during preparation of the sorbent, and reinforced the interaction between the sorbents and the analytes during the cleanup procedure. An ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) coupled with DPT-MSPE method has been developed to determine fifteen alkaloids in meat dishes and vegetable dishes. Under the optimal conditions, satisfactory recoveries, i.e., 83.4–125% for meat dishes and 84.2–122% for vegetable dishes, were obtained due to the high cleanup efficiency of the DPT-MSPE. Furthermore, the method, which displays good linearity (r ≥ 0.9991), acceptable precision (RSD < 8%), and low limits of quantification (0.054–1.058 ng g−1), has been successfully applied to several food samples, and it was confirmed that PAMAM@Mag-CNTs DPT-MSPE was a highly effective extraction method for alkaloids in cooked food samples.

Simultaneous determination of fifteen toxic alkaloids in meat dishes and vegetable dishes using double layer pipette tip magnetic dispersive solid phase extraction followed by UFLC-MS/MS

Enhanced cleanup efficiency hydroxy functionalized-magnetic graphene oxide and its comparison with magnetic carboxyl-graphene for PRiME pass-through cleanup of strychnine and brucine in human plasma samples.

The seeds of Strychnos nux-vomica L., as a traditional Chinese medicine, have good anti-inflammatory and analgesic activities. However, it usually leads to gastrointestinal irritation and systemic toxicity via oral administration. In the study, it was discovered that a novel gel transdermal delivery system contained brucine, the main effective component extracted from Strychnos nux-vomica. Results showed that the brucine gel system inhibited arthritis symptoms and the proliferation of the synoviocytes in the rat adjuvant arthritis model, which indicated its curative effect for rheumatoid arthritis. Meanwhile, it significantly relieved the xylene-induced ear edema in the mouse ear swelling test, which manifested its anti-inflammatory property. Moreover, the brucine gel eased the pain of paw formalin injection in the formalin test, which demonstrated its analgesic effects. In addition, the brucine significantly inhibited lipopolysaccharide (LPS)-induced Prostaglandin E2 (PGE2) production without affecting the viability of cell in vitro anti-inflammatory test, which proved that its anti-inflammatory and analgesic actions were related to inhibition of prostaglandin synthesis. It is suggested that the brucine gel is a promising vehicle for transdermal delivery on the treatment of inflammatory disease.

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

Abstract This research aimed to investigate how the relationship between counter ion and diacerein (DCN) exerts an effect on the skin penetration of DCN ion-pair compounds. After the ion-pair compounds were formed by DCN and organic amines with different functional groups, the hydrogen bond of these compounds was confirmed by Fourier-transform infrared (FTIR) spectroscopy and molecular docking. The skin of porcine ears was employed to conduct the in vitro skin penetration, DCN – triethanolamine was the most potential candidate with the Q 24h of 7.89 ± 0.38 µg/cm2 among organic amines with different functional groups. Whereas among the homologous fatty amine, the most permeable compound was DCN – lauryl amine with the Q 24h of 11.28 ± 0.48 µg/cm2. Molecular simulation was employed to explore the relationship between counter ion and DCN. It was revealed by the bind energy curve that DCN had the strongest compatibility with triethanolamine among organic amines and laurylamine (N12) among fatty amines. It was amazingly found that the in vitro permeation fluxes of DCN ion-pair compounds would increase with enhancing the compatibility of counter ion and DCN. These findings broadened our understanding of how the relationship between drug and counter ion affects the skin penetration of ion-pair compounds.

https://www.tandfonline.com/doi/pdf/10.1080/10717544.2022.2032877?needAccess=true

Huaibo Tang

Papers

A Novel Brucine Gel Transdermal Delivery System Designed for Anti-Inflammatory and Analgesic Activities.

Ion-pair compounds of diacerein for enhancing skin permeability in vitro: the compatibility–permeability relationship of counter ion and diacerein