Temperature sensitive nanogels for drug delivery and methods to improve nanoparticle recovery Sarah Hutchinson, Jonathan T. Peters, and Nicholas A. Peppas Department of Chemical Engineering, Department of Biomedical Engineering Biomaterials, Drug Delivery and Regenerative Medicine The University of Texas at Austin, Austin, TX 78712 Targeted Drug Delivery Solubility of fluorescein and PNIPMAAm/PPhMA Challenges/Future Work Introduction and Scope of Work Thermoresponsive nanogels Temperature sensitive polymers improve drug efficiency by facilitating delivery to targeted area within a desired concentration and time interval. Nanogels such as Poly(N-isoproyl acrylamide) (PNIPAAm) entrap drugs and act as nanocarriers. PNIPAAm encapsulates and carry drug to target tumor cells. EPR facilitates retention of encapsulated drug in tumor vasculature. Surface modifications increase LCST ≈ 40 °C After reaching target tumor cells, an external stimulus: Heats PNIPMAAm above LCST Collapses nanogel network Forces drug out Objective The current challenge is determining a reproducible and convenient methods for drug loading that will achieve high entrapment and nanoparticle recovery. EtOH has shown high solvent volumes to dissolve PNIPMAAm/PPhMA DMF dissolves polymer moderately but current dialysis bags (Spectra/Por Regenerated Cellulose) have limited exposure. Future work is to measure the effectiveness of dialysis to load therapeutic drugs. Determine drug loading efficiency of fluorescein in the PNIPMAAm/PPhMA (per solven) Determine the nanopartical yield 1. Na, K., Hee Lee, K., Haeng Lee, D., & Han Bae, Y. (2006). Biodegradable thermo-sensitive nanoparticles from poly(lactic acid)/poly(ethylene glycol) alternating multi-block copolymer for potential anti-cancer drug carrier. European Journal of Pharmaceutical Sciences, 27, 115-122. 2. Lyon, A. L. (n.d.). “Smart Nanoparticles” stimuli sensitive hydrogel particles. Lecture presented at Georgia Institute of Technology. 3. Zhang, Z., & Feng, S.-S. (2006). Self-assembled nanoparticles of poly(lactide)-Vitamin E TPGS copolymers for oral chemotherapy. International Journal of Pharmaceutics, 324, 191-198. 4. Sanson, C., Christophe, C., Le Meins, J., Soum, A., Thevenot, J., Garanger, E., & Lecommandoux, S. (2010). A simple method to achieve high doxorubicin loading in biodegradable polymersomes. Journal of Controlled Release. http://10.1016/j.jconrel.2010.07.123 Acknowledgements I want to thank my research mentor Jonathan Peters for teaching me about his research and encouraging me to ask questions that would help me design my own experiment. References Stimul us PEG Tumor cells PNIPMAAm gel network Drug T>LCST Problematic Drug Release Toxic Level Desirable – Controlled Release Minimum effective level Time Stimul us Solvent Testing Experiment Compare the drug loading efficiency and nanoparticle recovery between three solvents via dialysis. Dialysis is a drug loading technique that is simpler than other methods because it avoids stabilizers and emulsifiers. Fluorescein was substituted for the doxorubicin and PNIPMAAm/PPhMA (core/linker) was used for nanoparticle EtOH DMSO DMF Methods 1) Test solubility of fluorescein in solvents by adding solvent to known amount of fluorescein. EtOH DMSO DMF EtOH DMSO DMF 1:100 NP:fluroescein 1:10 NP:fluroescein 1:1 NP:fluroescein 2) For each solvent test three ratios of NP to fluorescein 3) Dialyze each homogenous solution against filtered water Synthesis of Thermo-responsive nanoparticles Ammonium Persulfate (APS) Initiator NIPAAm N’N’- Methylene-bis-acrylamide (MBAAm) Sodium dodecyl sulfate (SDS) Monomer Surfactant Crosslinker Inject APS/water solution and react for 6 hours Dialysis against water for 3 weeks Dissolve NIPMAAm MBAAm, SDS in filtered water in round bottom flask Heat solution to 70 °C in an oil bath and N 2 purge for 30 min (presence of O2 stops reaction)