(600c) Controlled Delivery of Paclitaxel and Heat From Poly(β-amino ester)-Based Magnetic Hydrogel Nanocomposites for the Treatment of Cancer

This research investigates the utilization of poly(β-amino ester) (PBAE) polymers and iron oxide for combined chemotherapeutic and heat delivery for hyperthermia-based treatment of cancer. Hyperthermia, the heating of cancerous tissue from 42 to 45°C, has been shown to increase the efficacy of conventional cancer therapies such as irradiation and chemotherapy. Currently, one of the challenges in using hyperthermia for cancer treatment is to restrict heating to only the tumor without damaging the healthy tissues surrounding the tumor site. The use of hydrogel nanocomposites that can deliver both heat and chemotherapeutic drugs directly to cancerous tissue can potentially overcome this obstacle. The hydrogel nanocomposites in this work provide a drug delivery vehicle (i.e., via the degradable PBAE polymer network) the ability to be heated remotely upon exposure to an alternating magnetic field (i.e., via the iron oxide nanoparticles). PBAE degradable polymers are finding a broad range of applications as drug delivery vehicles, tissue-engineering scaffolds, and in the fabrication of microdevices. These polymers consist of acrylate-terminated poly(β-amino ester)s that are synthesized via a condensation reaction that combines primary or secondary amines with diacrylates. The hydrogel networks degrade over time via hydrolysis of ester groups in the polymer backbone. One significant advantage of PBAE hydrogel nanocomposites is that they can be polymerized in situ without unnecessary harmful solvents which may allow them to be used as injectable materials in areas where surgical resection of tumors is not possible. Another advantage of these systems is the tailorability of the degradation of the PBAE polymers through the macromer chemistry and molecular weight.

PBAE marcomers comprised of poly(ethylene glycol) (n=400) diacrylate (PEG400DA) or diethylene glycol diacrylate (DEGDA) with isobutylamine (IBA) have been synthesized via a condensation reaction with various diacrylate to amine ratios. The macromers were analyzed via gel permeation chromatography to determine their molecular weight and polydispersity. For PEG400DA:IBA systems, molecular weight decreased with increasing diacrylate to amine ratio (2844 for 1:1.4 ratio and 2755 for 1:1.6 ratio) whereas the polydispersity stayed approximately the same at 1.45. 1:1.2 DEGDA:IBA exhibited a molecular weight of 2206 and polydispersity of 1.87. Hydrogel nanocomposites of pure and mixed PBAE macromers were fabricated via polymerization of the PBAE macromers with 5 weight % iron oxide and 2 weight % ammonium persulfate as the free radical initiator. Degradation of the hydrogel nanocomposites was carried out in phosphate buffered saline solution at 37°C. 1:1.2 DEGDA:IBA exhibited complete degradation after 7 weeks where as the studies for PEG400DA:IBA are underway. Ongoing investigation of these systems include the delivery of paclitaxel from the hydrogels, heating studies exposing the systems to an alternating magnetic field, cytotoxicity studies, and combined exposure of paclitaxel and heat from the hydrogel nanocomposites to M059K glioblastoma and MDA MB 231 breast adenocarcinoma cell lines. Overall, the tailorability and degradable nature of the PBAE hydrogel nanocomposites makes them solid candidates for combined hyperthermia and chemotherapy-based treatment of cancer.

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