1. Microfluidic Synthesis of Polymeric Nanoparticles Rohit Karnik Department of Mechanical Engineering Massachusetts Institute of Technology October 25, 2007

2. Acknowledgements Frank Gu, Pamela Basto, Chris Cannizzaro, Suman Bose, Eliza Vasile Omid Farokhzad Robert Langer MTL staff NIH

3. Targeted polymeric nanoparticles Versatile carriers Targeting capability FDA approved polymers Controlled release Tunable properties PLGA PEG + NH 2 Add to water + EDC/NHS Drug Nanoprecipitation Aptamer Nanoparticle Targeted nanoparticle Nanoparticle Farokhzad, et al. PNAS (2006)

4. Challenges Uptake by organs such as liver and spleen Optimization required –Size –Surface characteristics –Charge –Targeting moieties Batch-to-batch variation Polydispersity

5. Single step nanoparticle synthesis Single step synthesis Precursor composition  nanoparticle properties PLGA PEG + NH 2 PLGA PEG APT

6. Controlled precipitation Purification High Throughput Screening Advantages of microfluidic synthesis wwfwf Polymeric solution Water Formation of nanoparticles by nanoprecipitation Nanoparticles out Rapid mixing and homogenization  Controlled nanoprecipitation Combinatorial synthesis  Screening and optimization Other advantages  On-chip purification, scale up

7. Mixing by hydrodynamic flow focusing w wfwf PLGA-PEG in acetonitrile Water Formation of nanoparticles by nanoprecipitation Nanoparticles out Approximate flow profile Width of focused stream Mixing timescale Typical timescale ~ 0.5 to 5 ms

8. Effect of mixing time NucleationGrowth by insertion and aggregation Barrier to insertion Johnson and Prud’homme PRL 2003

9. Effect of mixing time Johnson and Prud’homme PRL 2003

10. Nanoprecipitation by flow focusing Syringe pump to control flow rate Device Nanoparticles

11. Nanoprecipitation by flow focusing TEM Image- Eliza Vasile

12. Effect of flow ratio on nanoparticle size (1/R)  mix ~0.04 ms  mix ~0.4 ms  mix ~3000 ms

13. Effect of flow ratio on nanoparticle polydispersity Faster mixing

14. Sensitivity of polymer composition to mixing time

15. Effect of mixing time and polymer composition on drug loading

16. Future Work Characterize effects of mixing time and precursor composition Design automated system for controlled combinatorial synthesis and screening

17. Thank you!