Chemical engineering of nanogel drug carriers: Increased bioavailability and decreased cytotoxicity

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Serguei V. Vinogradov, vinograd@unmc.edu, Ekta Kohli, Arin Zeman, and Alexander V. Kabanov, akabanov@unmc.edu. Center for Drug Delivery and Nanomedicine & Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-5830
Polymeric nanogel carriers significantly enhanced stability and biological activity of encapsulated nucleotide and oligonucleotides. Chemical engineering of nanogel structure could increase bioavailability and decrease cytotoxicity of nanogels. Pluronic®-based nanogels were obtained with good yields and small particle size using a novel micellar synthesis. Preparation of nanogels from a biodegradable PEI resulted in significantly less toxic carriers. Nanogel network contained disulfide bonds readily degraded following treatment with reducing agent. Degradation products expected to have a lower toxicity and better clearance than nanogels. Cellular accumulation of nanogels increased in the following order PEG