Transdermal delivery of colchicine using dissolvable microneedle arrays for the treatment of acute gout in a rat model

Abstract

Colchicine (Col) is used to prevent and treat acute gout flare; however, its therapeutic use is strictly limited owing to severe gastrointestinal side effects after oral administration. Therefore, we developed a dissolvable Col-loaded microneedle (MN) with hyaluronic acid to deliver Col via the transdermal route. We studied the preparation, mechanical properties, skin insertion, skin irritation, drug content, and transdermal release of the Col-loaded MN. The pharmacokinetics of Col after Col-loaded MN application were compared with those of Col solution gavage over 24 h. Knee joint edema evaluation and the hindfoot mechanical threshold test were conducted to determine the pharmacodynamic profile. The dissolvable Col-loaded MN possessed sufficient mechanical strength to penetrate the skin and release the loaded drug. No skin irritation was observed for 3 days after application. We found that 3.36-fold more Col contained in MNs was delivered through the skin compared with that in gel in vitro , and moderate relative bioavailability in vivo . The Col-loaded MN significantly relieved swollen knee joints and mechanical hypernociception in an acute gout model in rats. The dissolvable Col-loaded MN array reduced inflammation and pain via topical administration when acute gout occurred. Reducing the gastrointestinal side effects of Col-loaded MNs is expected to optimize the therapeutic effects of Col and improve patient compliance.

Delivery Strategies for Colchicine as a Critical Dose Drug: Reducing Toxicity and Enhancing Efficacy

“…* indicates statistical significance at p < 0.05, n = 3; (Reprinted with permission from Ref. [ 33 ]. Copyright © 2022 Taylor & Francis group).…”

Microneedles a Possible Successor Technology for Tdds: A Patent Analysis

“…The device includes a handle, a treatment head, and a meibomian gland drug delivery patch [136]. Tamayol Ali et al, the invention relates to wound healing formulations and method which consists of microneedle arrays and devices for treating wounds and bacterial infections [144].…”

Intestinal toxicity alleviation and efficacy potentiation through therapeutic administration of Lactobacillus paracasei GY-1 in the treatment of gout flares with colchicine

“…19 However, to the best of our knowledge, there has been no investigation into detoxifying COL by probiotics when treating gout flares, although many effects have been made to reduce its toxicity. [20][21][22] Here, we were amazed to discover that GY-1 effectively alleviates the physical, behavioral, and intestinal toxicity caused by COL. Additionally, we made an intriguing discovery that GY-1 enhances therapeutic effects in treating gout flares with COL. Furthermore, the absolute quantification of the 16S rRNA gene reveals that GY-1 restores the gut microbiota imbalance caused by COL.…”

“…19 However, to the best of our knowledge, there has been no investigation into detoxifying COL by probiotics when treating gout flares, although many effects have been made to reduce its toxicity. 20–22…”