Introduction 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. Objectives 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. Methods 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. Results 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. Conclusion 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.

Efficient and synchronized co-delivery of active pharmaceutical ingredients (APIs) from classical Traditional Chinese Medicine (TCM) formulae is crucial for exerting their synergistic therapeutic effects. However, constructing dual-drug-loaded systems capable of controllably delivering APIs with divergent polarities remains challenging due to differences in molecular weight and solubility among constituents. In this study, paeoniflorin (PAE) and glycyrrhizic acid (GLA)-active ingredients derived from the renowned TCM formula Shaoyao Gancao Decoction-were selected as model compounds. To address the co-loading and synchronized delivery of hydrophilic PAE and hydrophobic GLA, we developed a β-glycerophosphate disodium salt (β-GP)/hydroxypropyl cellulose (HPC) hydrogel. This hydrogel uniquely combined skin-triggered sol-gel transition with electrostatically enhanced solubility for GLA, and was subsequently fabricated into a microneedles (MNs) formulation. Confocal laser scanning microscopy confirmed uniform distribution of both drugs within the MNs, despite their contrasting polarities. In vitro transdermal studies revealed that the MNs significantly outperformed the hydrogel in terms of delivery efficiency. Release kinetics followed the Higuchi model, with cumulative release rates at 72 h reaching 38.84 ± 0.52 % for PAE and 44.26 ± 4.38 % for GLA, indicating synchronized release. This platform represents an innovative strategy for achieving the synchronized, efficient, and sustained delivery, holding significant promise for advancing the development of TCM formulations.

Lipophilic drugs loaded into hydrogel vehicles for controlled release often encounters drawbacks such as low loading capacity, tedious inclusion methods and invalidity caused by syneresis. Facing this issue, we proposed a non-solvent drug loading system, thermal-grinding supramolecular network (TGSN), in which the monomer, crosslinker and drug molecules in solid state were grinded and then subjected to melting gelation. Paeonol, with a poor water solubility of 0.54 mg/mL, was chosen as a model drug. Both organosulfur-based polymeric network and paeonol aggregates constituted the main structure of TGSNs. Thus, the network had special properties such as stretchability, anti-swelling, elasticity, antibacterial activity, surface hydrophilicity, self-healing and adhesion. In vitro cellular toxicity assay demonstrated that TGSN improved L929 cell proliferation with minimal cytotoxicity. Viewed by transdermal release assay, TGSN could achieve sustained release of paeonol. Proved by skin eczema model in Kunming mice, TGSN possessed an excellent therapeutic effect and a low recurrence probability.

Poor transdermal permeability limits the possibility of most drug delivery through the skin. Auxiliary permeable microneedles (AP-MNs) with a three-dimensional network structure can effectively break the skin stratum corneum barrier and assist in the transdermal delivery of active ingredients. Herein, we propose a simple method for preparing AP-MNs using polyvinyl alcohol and Eudragit NM30D for the first time. To optimize the formulation of microneedles, the characteristics of swelling properties, skin insertion, solution viscosity, and needle integrity were systematically examined. Additionally, the morphology, mechanical strength, formation mechanism, skin permeability, swelling performance, biocompatibility, and in vitro transdermal drug delivery of AP-MNs were evaluated. The results indicated that the microneedles exhibited excellent mechanical-strength and hydrogel-forming properties after swelling. Further, it proved that a continuous and unblockable network channel was created based on physical entanglement and encapsulation of two materials. The 24 h cumulative permeation of acidic and alkaline model drugs, azelaic acid and matrine, were 51.73 ± 2.61% and 54.02 ± 2.85%, respectively, significantly enhancing the transdermal permeability of the two drugs. In summary, the novel auxiliary permeable microneedles prepared through a simple blending route of two materials was a promising and valuable way to improve drug permeation efficiency.

With the thriving of mussel-inspired polyphenol chemistry as well as the demand for low-cost analogues to polydopamine in adhesive design, tannic acid has gradually become a research focus because of its wide availability, health benefits and special chemical properties. As a natural building block, tannic acid could be used as a crosslinker either supramolecularly or chemically, ensuring versatile functional polymeric networks for various applications. Up to now, a systematic summary on tannic-acid-based networks has still been waiting for an update and outlook. In this review, the common features of tannic acid are summarized in detail, followed by the introduction of covalent and non-covalent crosslinking methods leading to various tannic-acid-based materials. Moreover, recent progress in the application of tannic acid composites is also summarized, including bone regeneration, skin adhesives, wound dressings, drug loading and photothermal conversion. Above all, we also provide further prospects concerning tannic-acid-crosslinked materials.

Making a hydrogel-based first-aid bandage with green resources, desirable biocompatibility, universal adhesive properties, low cost and simple production is a long-standing research aspiration. Considering this, three naturally existing organic acids, namely tannic acid, thioctic acid and phytic acid, were used to construct a novel adhesive gel (TATAPA hydrogel) for epidermal tissue bandage applications. This hydrogel could be synthesized under mild conditions with no need for a freeze-thawing shaping procedure, and was transparent, moldable and stretchable with good stability under continuous water immersion. In lap-shear tests, the TATAPA hydrogel could adhere to various hydrophilic and hydrophobic surfaces. Moreover, in the case of skin tissue adhesion, the hydrogel could be easily peeled off from the skin, meeting wearability requirements. Rheological tests showed that the hydrogel possessed thermal sensitive properties derived from multi-supramolecular interactions. The methicillin-resistant Staphylococcus aureus (MRSA)-infected burn wound test demonstrated that the hydrogel had desirable antibacterial activity and was beneficial for wound healing. A femoral artery bleeding assay was also used to reveal that the TATAPA hydrogel could be directly pasted onto the bleeding site for hemostasis. Overall, this hydrogel demonstrates potential as a surgical bioadhesive for a broad range of medical applications.