Study on spatial and temporal control of drug delivery using biocompatible materials

Abstract

In this dissertation, the biocompatible drug delivery systems with spatially or temporally controlled drug release were developed for the treatment of rheumatoid arthritis and solid tumor immunotherapy. In chapter 2, we dealt with the study of rheumatoid arthritis (RA) treatment through spatial control of drug delivery using porous silicon particle-based nanoparticles. Using the inflammatory properties in RA tissue, calcium silicate-coated porous silicon nanoparticles showed spatially controlled drug delivery due to the size and spatially controlled drug release using the pH dependent dissolution of calcium silicate. Also, the dissolution by-products of particles promoted the regeneration of damaged bone tissue and inhibited the division of inflammatory T cells. By the synergistic effect of these strategies, methotrexate-loaded porous silicon-based nanoparticles enhanced the efficacy of the drug with less off-target toxicity and promoted the regeneration of damaged bone tissue. While the existing RA nanomedicines work as a drug carrier, our developed nanomedicine is not only a drug carrier but also the particle itself works as a therapeutic agent against damaged bone tissue.In chapter 3, we dealt with the study of solid cancer immunotherapy through temporal control of drug delivery through porous silicon-based microparticles. By engineering the three-layered pore structure of porous silicon, the sequential drug release and time-controlled release of adjuvants and various therapeutic antibodies become possible. For combination therapy of two different therapeutic antibodies which have to be administered in sequential, two different porous silicon-based microparticles were developed by simple change of the pore structures. Intratumoral injection of two microparticles showed superior antitumor effect on immunosuppressive solid tumors compared to conventional concurrent treatment and even three sequential injections with each drug. patients will be less burdened. This drug delivery system is considered to be applicable to various diseases and therapeutics drugs, which reduces the patient’s burden during treatment.In chapter 4, we dealt with the study of the efficient formation of the systemic antitumor immunity through spatial control of adjuvant delivery using micelle nanoparticles and their peritumoral administration. Compared to intratumoral administration of lipophilic adjuvant, peritumoral injection of micellar nanoparticles reduced the possibility of off-target toxicity by directly delivering adjuvants to not only tumor tissue but also tumor-draining lymph nodes. This resulted in increased systemic antitumor immunity and significant prevention of tumor recurrences.The findings in this study showed that porous silicon based and micelle-structured biocompatible materials have high utility in spatial or temporal drug release, and are effective in treating rheumatoid arthritis and solid cancer immunotherapy. Moreover, the biomaterials were confirmed to be biocompatible, and applicable to various drugs and disease because it is not limited to specific drugs, it is considered to have high potential for clinical use.