Synthesis of pH-responsive hydrogel thin films grafted on PCL substrates for protein delivery

Abstract

A new visible light induced graft polymerization method was utilized to prepare pH-sensitive hydrogel layers covalently attached to polymer substrates for drug delivery. In our strategy, isopropyl thioxanthone semi-pinacol (ITXSP) dormant groups were firstly introduced on the surface of a polycaprolactone (PCL) film by a UV-induced abstracting hydrogen-coupling reaction. Then visible light induced graft crosslinking polymerization was performed to initiate polymerization of poly(ethylene glycol) diacrylate (PEGDA) and acrylic acid (AA), resulting in the formation of a hydrogel layer. The thickness of the hydrogel film can be controlled by varying the exposure time and monomer composition. The grafted hydrogel layers showed a flat morphology and dense structure, which is different from the traditional reported porous structure. The water contact angle of the hydrogel layer exhibited a reversible change from 381 to 181 when the film was alternatively treated in buffers of pH 2.0 and 7.4, respectively. Patterned hydrogel layers were prepared as a model to determine the change in the height of the grafted hydrogel layer as a function of pH. As the pH changed from 2.0 to 7.4, the hydrogel pattern showed an increase in height due to the swelling of the hydrogel network, and the hydrogel layer formed by 0.2 wt% PEGDA and 25 wt% AA showed the most increase (30%) in height. Bovine serum albumin (BSA) and lysozyme as models of protein drugs were incorporated in the hydrogel network, and their release also showed obvious pH-sensitivity. At pH 2.0, hydrogels present a faster initial burst release due to the squeezing mechanism. Tertiary structure analysis showed that encapsulation and release did not affect the protein conformation. These findings have improved our understanding of hydrogel thin films, which may be useful as potential vehicles of therapeutic proteins in drug delivery applications. Scheme 1 Schematic illustration of the synthesis of a P(PEGDA/AA)/ protein hydrogel thin layer on the PCL film. (a) ITXSP was immobilized on the surface of the PCL substrate under UV irradiation. (b) Hydrogel layer was formed under visible light irradiation. (a 0 ) and (b 0 ) are the reaction mechanisms for steps (a) and (b), respectively.

PVA/Carbon Dot Nanocomposite Hydrogels for Simple Introduction of Ag Nanoparticles with Enhanced Antibacterial Activity

“…Hydrogels, as a kind of soft‐wet material that composed of a large amount of water and 3D networks of polymer chains, have been widely applied to various biomedical areas, such as tissue engineering scaffolds, drug carriers, and drug release, vehicles, scaffolds for cell cultures, biosensors, and wound dressings . In particular, polyvinyl alcohol (PVA) hydrogel has been widely studied and well demonstrated to be an ideal biomaterial due to its excellent mechanical properties, biocompatibility, and low water absorption abilities .…”

Preparation of a Salecan/poly(2‐acrylamido‐2‐methylpropanosulfonic acid‐co‐[2‐(methacryloxy)ethyl]trimethylammonium chloride) Semi‐IPN Hydrogel for Drug Delivery

“…Therefore, no detectable impurities were generated by this delivery vehicle, and the insulin was released from the gel matrix in its original form. These results suggest that our strategy to encapsulate insulin is effective, and that insulin itself was not altered during the synthesis, incorporation, and release processes …”

“…It is crucial that the fabricated drug release vectors not only deliver the drug in a predictable manner, but also preserve its activity . Typically, drug denaturation may occur during the preparation, storage, and release periods . Figure D reveals the UV/Vis absorption spectra of released and standard insulin.…”

“…The remaining insulin solution and the phosphate buffer used to rinse the drug‐loaded hydrogels were collected together. The content of drug remaining in the soaking solution was estimated using the Bradford assay kit by UV/Vis spectrophotometry (TU‐1900, China) at 595 nm . The drug loading efficiency (DLE) was measured according to the following Equation : …”

Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility

“…Obviously, the key process for stably attaching hydrogel layers onto substrate surfaces is to create sufficient anchoring sites for hydrogel layers, and many methods have been developed. For example, Zhang et al immobilized isopropyl thioxanthone semipinacol dormant groups on polycaprolactone film surface as anchoring sites . Yuk et al introduced double bonds onto various solid surfaces as anchoring sites by the reaction of silane 3‐(trimethoxysilyl) propyl methacrylate .…”