Polymers for Health 7

Synthesis of hollow nanoparticles via inverse miniemulsion periphery polymerization for drug delivery applications

Investigators:
Prof Martina Stenzel
Prof Per B. Zetterlund

Polymeric nanoparticles (normal diameter range 50 – 500 nm) find a number of biomedical applications, e.g. drug delivery.  Hollow nanoparticles (nanocapsules) with an aqueous (hydrophilic) interior are particularly attractive for the delivery of water soluble drugs such as proteins or vaccines.  The nanocapsules protect the drugs from decomposition, and the drugs are released only when the nanocapsules break down.  

One of the most common methods for preparation of polymeric nanoparticles is polymerization in a dispersed (heterogeneous) system.  In the simplest of terms, this means that polymerization occurs in monomer/polymer particles that are dispersed in water with the aid of surfactants.  There are various such techniques available, each associated with specific advantages and disadvantages.  
A relatively new approach towards nanoparticle synthesis is the so called “miniemulsion periphery polymerization” method, which entails (i) creation of a miniemulsion (organic phase dispersed in water), and subsequently (ii) polymerization in the aqueous phase using a macroinitiator confined to the oil-water interphase, thus generating a “shell” with a liquid organic interior.  The technique has potential as offering superior control over final particle size, which is an important consideration in drug-delivery applications.  

This project is concerned with “inverse” miniemulsion periphery polymerization for the preparation of hollow polymeric nanoparticles for drug delivery. By the term “inverse” is meant that the continuous phase is organic (hydrophobic) and the dispersed phase is hydrophilic (e.g. water). The drug will be present in the dispersed phase, and polymerization is subsequently carried out around the periphery of this dispersed phase, thus generating a hollow particle by formation of a shell around the dispersed phase. Reversible addition-fragmentation chain transfer (RAFT) polymerization is employed to prepare shells of controlled microstructure.  

This approach has been tested for the encapsulation of proteins. The protein was located in the water pool in the centre of the hollow sphere. In this environment, the protein is protected from degradation, but it is also positioned in an aqueous environment that helps maintaining its crucial three-dimensional shape.

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Figure 1. TEM images of hollow nanoparticles (left and middle) synthesized via inverse miniemulsion periphery polymerization (RAFT) of MMA and EGDMA. Right: TEM of hollow spheres with protein located in the core

 

References

  • Synthesis of Hollow Polymeric Nanoparticles for Protein Delivery via Inverse Miniemulsion Periphery RAFT Polymerization, R. H. Utama, Y. Guo, P. B. Zetterlund and M. H. Stenzel, Chem. Commun., 2012, 48, 11103–11105.
  • Inverse Miniemulsion Periphery RAFT Polymerization: A Convenient Route to Hollow Polymeric Nanoparticles with an Aqueous Core, R. H. Utama, M. H. Stenzel, P. B. Zetterlund, Macromolecules 2013, 46, 2118−2127.