Lack of specificity in conventional chemotherapy leads to significant dose-limiting toxicities and requires patients to wait long periods between treatments. During this time, cancer cells can recover and develop drug resistance. To improve treatment and reduce toxicity to healthy tissues, we have developed novel, intelligent nanoscale hydrogel carriers (nanogels) for the targeted and controlled delivery of chemotherapeutic agents.<br/><br/>Here we show that the nanogel molecular architecture can be tailored to carry a variety of cargos with varying physicochemical properties, and release can be tuned to a desired stimuli. The nanogels are comprised of: i) hydrophilic, cationic 2-(diethylamino)ethyl-methacrylate, ii) tetraethylene-glycol-dimethacrylate crosslinker, and iii) surface-grafted poly(ethylene-glycol). Impact of nanogel hydrophobicity was investigated through systematic variation of monomer steric bulk and chain length. The physical properties of the resulting nanogels were compared using dynamic light scattering, zeta potential, titration, pyrene fluorescence, and red blood cell hemolysis to elicit the influence of polymer composition on swelling ratio, surface charge, pKa, hydrophile-hydrophobe phase transition, and erythrocyte membrane disruption capability. The delivery capacity was analyzed using multiple agents.<br/><br/>We demonstrated that both the grafted and hydrophobic monomer composition can be varied to enable precise control over the nanogel surface and core characteristics to enable effective, controlled delivery. Varying both chain length and steric bulk allowed for precise control over the thermodynamic response (swelling ratio), dynamic behavior (pKa, membrane disruption), and drug-polymer interaction (delivery capacity). Ultimately, we demonstrated that the tunability of our multicomponent nanogel can be exploited to enable long-circulation and effective transport of the drugs to the tumor site.

Engineering intelligent hydrogel nanoparticles with tunable release properties

255th National Meeting (2018)

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