"Smart" Delivery of Monoclonal Antibodies from a Magnetic Responsive Microgel Nanocomposite.

ABSTRACT

"Smart" drug-delivery systems have significant potential to increase therapeutic efficiency, avoid undesired immune responses, and minimize drug side effects. Herein, we report on an innovative strategy to control the drug release process using two magneto-activated materials operating in the system. One of them, a polyvinyl alcohol (PVA)-diboronate (DB)-interpenetrated (IPN) alginate (Alg) microgel nanocomposite (PVA-DB-IPN-Alg) loaded with magnetic nanoparticles (MNPs), is acting as a drug-delivery system. The drugs or model (bio)molecules are loaded in the PVA-DB-IPN-Alg and then released upon receiving a magnetic signal. Another component of the system is represented with the MNPs functionalized with the glucose oxidase (GOx) enzyme, GOx-MNPs. The immobilized GOx biocatalytically produces H2O2 in the presence of glucose and oxygen, while the PVA-DB-IPN-Alg is decomposed/dissolved by reacting with H2O2. In the absence of a magnet, the biocatalytically produced H2O2 was mostly decomposed by the catalase enzyme present in the solution, thus not reaching the alginate microgel. Upon aggregation of these two types of particles induced by a magnet, the GOx-MNPs produced H2O2in situ increasing locally its concentration, degrading the PVA-DB-IPN, thus opening pores in the alginate hydrogel resulting in a faster release of the entrapped payload. The release of the payload was confirmed in physiological complex environments, exemplified with human serum, demonstrating the stability and functionality of the materials in biological fluids. The release rate was strongly dependent on the concentration of catalase but not dependent on glucose concentration. The magneto-induced release process was confirmed for the small model protein payload, such as bovine serum albumin (BSA), as well as the trastuzumab monoclonal antibody (TmAb). For the latter, the release rate was up to 3.3 times higher in the presence of the magnet than in the absence of it in the human serum. We expect that the drug-delivery concept developed by these materials can find useful applications in the emerging field of "smart" materials in immunotherapy.