Non-solvent cinnamic acid-based gel patch for transdermal drug delivery

• Based on the concept of non-solvent transdermal patch for drug delivery, cinnamic acid was directly loaded into thioctic acid-zinc ions polymeric network. The corresponding synthetic route was facile, robust and low-cost. • The gel patch in this research joined the merits of cinnamic acid and polymer substrate. For instance, the gel integrated multiple properties such as tissue adhesion, underwater adhesion, antibacterial, viscoelasticity, self-healing, anti-swelling, recyclability, biocompatibility, anti- inflammation, sustained drug release, among others. • Metal acetates could also functioned as a building block for poly(thioctic acid)-based materials, resulting in a non-solvent supramolecular gel system. • The cinnamic acid-thioctic acid-zinc ions gel could be used as a new therapy for open-wound healing, bleeding and acute myocardial ischemia. Drugs entitled polymeric network special functions in bio-applications. However, the introduction of appropriate solvent for drugs generally incurred tedious inclusion methods, intensive chemical design and aging caused by solvent loss. Herein, a novel non-solvent gel system was proposed for water-insoluble drug loading and subsequent controlled transdermal drug release. The purpose of this work is related to prepare a non-solvent transdermal gel patch loaded with cinnamic acid (CA) for the treatment of myocardial ischemia (MI), wound healing, etc. The non-solvent transdermal gel patch was easily synthesized by melting the mixture of CA, thioctic acid (TA) and zinc acetate dihydrate. Basic gel properties such as chemical architecture, mechanical strength, swelling property, rheology, adhesive property, surface hydrophilicity and antibacterial activity were studied. Biocompatibility was evaluated by in vitro NIH3T3 cell culture and in vivo subcutaneous implantation. Transdermal drug delivery was revealed by a HPLC method for in vitro transdermal assay. A SD rat dorsal full-thickness open wound model and a SD rat MI model were involved to verify the therapeutic effect of this gel patch. The prepared gel patch contained both physical crosslinking and chemical crosslinking points. As viewed by mechanical and rheological tests, the gel exhibited ductility, viscoelasticity and self-healing property. The gel showed wide-scope adhesion towards various materials, in which the maximum tissue adhesion strength reached 0.12 MPa. The transdermal CA release rate was ranged from 20 to 40 µg/h. In prospect of histological analysis from MI treatment, this gel was also capable of repairing myocardial injury, promoting angiogenesis and inhibiting myocardial cell hypertrophy. This work opened an approach in the field of gel patch design for transdermal drug delivery, which was promising in large scale production and biomedical applications.