Soluplus®-based dissolving microarray patches loaded with colchicine: towards a minimally invasive treatment and management of gout.
Qonita Kurnia AnjaniAkmal Hidayat Bin SabriNatalia Moreno-CastellanosEmilia UtomoÁlvaro Cárcamo-MartínezJuan Domínguez-RoblesLuki Ahmadi Hari WardoyoRyan F DonellyPublished in: Biomaterials science (2022)
Considered as one of the most common inflammatory arthritis, gout is characterised by a sudden onset of severe joint pain. As the first-line drug of choice used in treating acute gout, colchicine (CLC) is hindered by poor gastrointestinal permeability as well as unfavourable gastrointestinal side effects. Herein, we present, for the first time, the preparation of microarray array patches (MAPs) made of a polymeric solubiliser, Soluplus®, loaded with CLC for its systemic delivery. The fabricated MAPs displayed acceptable mechanical properties and were capable of being inserted into the skin to a depth of ≈500 μm in full thickness ex vivo neonatal porcine skin, as evidenced by optical coherence tomography. In vitro dermatokinetic studies utilising full thickness neonatal porcine skin demonstrated that the CLC-loaded MAPs delivered CLC across all skin strata, resulting in a delivery efficiency of 73% after 24 hours. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell proliferation assays along with LIVE/DEAD™ staining on the 3T3-L1 cell line showed that the MAP formulation displayed minimal toxicity, with acceptable biocompatibility. Lastly, the anti-inflammatory properties of the formulation were evaluated using a THP-1 macrophage cell line. It was shown that treatment of THP-1 macrophages that are exposed to lipopolysaccharide (LPS) with CLC-loaded MAPs caused a significant ( p < 0.05) reduction of TNF-α production, a pro-inflammatory cytokine typically associated with the early onset of acute gout. Accordingly, CLC-loaded MAPs could represent a new minimally-invasive alternative strategy for management of acute gout.
Keyphrases
- drug delivery
- wound healing
- early onset
- optical coherence tomography
- uric acid
- minimally invasive
- cancer therapy
- liver failure
- drug induced
- soft tissue
- respiratory failure
- cell proliferation
- anti inflammatory
- inflammatory response
- late onset
- rheumatoid arthritis
- oxidative stress
- drug release
- metabolic syndrome
- aortic dissection
- pain management
- adipose tissue
- chronic pain
- spinal cord injury
- high density
- robot assisted
- toll like receptor
- combination therapy
- cell cycle
- acute respiratory distress syndrome
- immune response
- pi k akt
- neuropathic pain
- smoking cessation
- optic nerve
- extracorporeal membrane oxygenation
- electronic health record