Abstract

Several temporarily stable polymer micelle systems that might be used as ultrasonic-activated drug delivery carriers were synthesized and investigated. These polymeric micelle systems were Plurogel®, Tetronic®, poly(ethylene oxide)-b-poly(N-isopropylacrylamide) and poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactaten). In previous work in our lab, Pruitt et al. developed a stabilized drug carrier named Plurogel® [5, 6]. Unfortunately, the rate of the successful Plurogel® synthesis was only about 30% by simply following Pruitt's process. In this work, this rate was improved to 60% by combining the process of adding 0.15 M NaCl and/or 10 µl/ml n-butanol and by preheating the solution before polymerization. Tetronics® were proved not to be good candidates to form temporarily stable polymeric micelle system by polymerizing interpenetrating networks inside their micelle cores. Tetronic micelle systems treated by this process still were not stable at concentrations below their critical micelle concentration (CMC). Poly(ethylene oxide)-b-poly(N-isopropylacrylamide)-N,N-bis(acryloyl)cystamine micelle-like nanoparticles were developed and characterized. When the N,N-bis(acryloyl)cystamine (BAC) was from 0.2 wt% to 0.75 wt% of the mass of poly(N-isopropylacrylamide), diameters of the nanoparticles at 40ºC were less than 150 nm. The cores of the nanoparticles were hydrophobic enough to sequester 1,6-diphenylhexatriene (DPH) and the anti-cancer drug doxorubicin (DOX). Nanoparticles with 0.5 wt% BAC stored at room temperature in 0.002 mg/ml solutions were stable for up to two weeks. Poly(ethylene oxide)-b-poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate-lactaten) micelle systems were synthesized and characterized. The degree of polymerization of lactate side group, n, was 3 or 5. The copolymers with N-isopropylacrylamide:2-hydroxyethyl methacrylate-lactate3: poly(ethylene oxide) (NIPAAm:HEMA-lactate3:PEO) ratios of 20.0:5.0:1 or 22.5:2.5:1 and with NIPAAm:HEMA-lactate5:PEO ratios of 17.5:7.5:1, 20.0:5.0:1 or 22.5:2.5:1 produced micelles stable about 2 days at 40°C. The cores of the micelles were hydrophobic enough to sequester DPH and DOX. The DOX release from the micelles having molar ratio of NIPAAm:HEMA-lactate3:PEO equal to 20.0:5.0:1 was about 2 % at room temperature and 4 % at body temperature. This system is a possible candidate for ultrasonically activated drug delivery.

Degree

PhD

College and Department

Ira A. Fulton College of Engineering and Technology; Chemical Engineering

Rights

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