(341h) Fabrication of Monodisperse Polyanhydride Nanoparticles by Microemulsion Polymerization

Biodegradable polyanhydrides have been conventionally synthesized with solution polymerization and used to fabricate 200-800 nm nanoparticles.¹ Particle size and size distribution is an important determinant of immune cell activation², and small (< 50 nm), uniform particles could be effectively used as drug or vaccine delivery devices and adjuvants. Microemulsion polymerization is a technique with which sub-50 nm polymer particles can be synthesized from monomer in one step via a free radical mechanism.³ In this work, the monomer sebacic acid dimethacrylate (MSA) has been used to synthesize crosslinked polyanhydrides using free radical polymerization.⁴ An inverse microemulsion system composed of MSA- and chloroform-swollen micelles stabilized by Span 80 in hexane was studied. The phase behavior of the system over a range of temperatures and compositions was determined visually. PolyMSA nanoparticles were then synthesized by microemulsion polymerization. The particle diameter was controlled by varying reaction times and monomer concentration, resulting in particles with diameters ranging from 20 nm to 300 nm. The particles were characterized by scanning electron microscopy and dynamic light scattering. Nuclear magnetic resonance (NMR) and monomer mass loss were used to determine polymerization rate. NMR was also used to determine distance between crosslinks. Hydrolytic degradation rates of polyMSA particles were compared to conventional polySA particles by measuring the diameters of the surface-degrading particles. The microemulsion polymerization technique offers a new approach to fabricating monodisperse particles with controlled sizes for applications in drug and vaccine delivery.

¹ B. Ulery, Y. Phanse, A. Sinha, M. Wannemuehler, B. Narasimhan, B. Bellaire, Pharm. Res. 2008, 26, 683-690.
² S. Reddy et al., Nat. Biotechnol. 2007, 25, 1159-1164.
³ M. Antonietti, T. Nestl, Macromol. Rapid Comm. 1994, 15, 111-116.
⁴ A. Weiner, E. Bock, M. Gipson, V. Shastri, Biomat. 2008, 29, 2400-2407.