Monday, November 5, 2007 - 1:10 PM
69c

Uni-Nanogel For Controlled Delivery Of Multiple Therapeutics

Gauri Misra, Surgery, Penn State University College of Medicine, 500 University Drive, Hershey, PA 17033, William Weiss, Surgery, MC H151, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, and Tao Lu Lowe, Surgery, Pennsylvania State University, 500 University Drive, Hershey, PA 17033.

Nanotechnology has emerged as an exciting area of science with a wide range of applications in biology, medicine, and pharmaceutics[1-4]. Polymer-based nanogels are of especial interest in drug delivery and diagnostic applications because of tunable chemical and physical properties. In this work, we report the synthesis, characterization, and drug releasing property of nanogels based on a monomer, N-isopropyl acrylamide (NIPAAM) or 2-hydroxyethylmethacrylate and a cross-linkable macromer, 2-hydroxyethylmethacrylate-lactate-dextran. The nanogels with varying mass ratios between the monomer and macromer were synthesized in aqueous medium using ultra-violet photo-cross-linking and characterized by dynamic light scattering method. The nanogels were found to be non-toxic to neuron-like PC 12 and R28 cells, and Blood Brain Barrier Vascular Endothelial Cells (BBBVECs) up to 500 ìg/mL concentration. Blood biocompatibility of the nanogels was evaluated by hemolysis test. The nanogels were non-hemolytic for at least 24 hr. Model therapeutic agents, such as heparin, low molecular weight heparin (LMWH), insulin, and FITC-dextran having molecular weights 15,000, 4,500, 5,600, and 4,000, respectively, were loaded into the nanogels during the synthesis process. Release of these therapeutic agents in PBS (pH 7.4) at 37 °C occurred at different time and onset of the release depended on the size and conformation of the therapeutic agents. Insulin was released faster than LMWH and FITC-Dextran. Almost no release of heparin was observed for four months, and only HEMA-macromer nanogel released heparin after eighty days. Thus, the developed nanogels have great potential to be used as nanodevices for controlling the release of multiple drugs. Further work on encapsulating multiple drugs into and releasing them from the nanogels is in progress.

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