General Science

Nanoparticle Aggregates    

  • Aggregates are nanoflex particles that adhere together forming a bulk solid.
  • Particles are not bound to each other; the surfaces have a physical attraction to each other.

Advantages

  • Biocompatible material.
  • Different routes of application and implantation methods.

Features

  • Wide range of physical properties. Hard to soft materials.
  • Tailorable drug delivery profiles.

Benefits     

  • Formulation flexibility allows incorporation in a broad range of applications.

Formulation Flexibility

  • Size of the particles and the physical properties of the resulting aggregate can be controlled during the synthesis.
  • The in vivo physical properties of the aggregates can be varied to provide material that behaves like adipose tissue, collagen or articular cartilage.
  • Molecules can be incorporated into the aggregates during formation for subsequent controlled release
    • Physical properties such as strength and porosity of the aggregates can be varied by changing the nanoparticle size and with subtle changes in the composition ratio of monomers used in polymerization and the crosslink density.

Nanoflex® particles vs. bulk hydrogel     

Nanoflex particles are smaller pieces of larger bulk hydrogels. Nanoparticles - 10-800 nm

Nanoflex® particles

  • Formed of hydroxy-terminated methacrylate monomers (identical to contact lens materials)
    • 2-hydroxyethylmethacrylate (HEMA)
    • 2-hydroxypropylmethacrylate (HPMA)
  • Aqueous Free Radical Polymerization.
  • Typically crosslinked by dimethacrylates.
  • Particles stabilized as a sol by surfactant.
  • Size and physical composition can be controlled during synthesis.

Nanoflex® phyical properties     

  • Aggregates allow deformation and can be molded.
  • Elasticity and modulus (stretching and “firmness”) can be varied to provide properties simulating materials such as cartilage or adipose tissue.

 

Synthesized in Powder, Liquid and Gel

1. Nanoparticle Powder Aggregate

2. Nanoparticle Injectable Aggregate     

  • Synthetic, inert biocompatible biomaterial with extensive history in FDA-Approved devices.
    • Contact lenses, implants.
  • Physical properties can be controlled by changing formulation variables,
    • Particle size
    • Crosslink density
    • Monomers and comonomers incorporated into formulation
  • Physical characteristics
    • Material can be soft, duplicating collagen or adipose tissue characteristics
    • Material can be hard, approaching articular cartilage
  • High water content promotes biocompatibility and cellular infiltration
  • Potential to avoid common problems associated with permanent dermal fillers
    • Granuloma
    • Acute immune response

3. Nanoparticle Viscous Gel Aggregate

  • Viscous gel composed of hydrogel nanoparticles suspended in water with biocompatible chemical composition.
  • Physical properties can be controlled by changing formulation variables.
    • Particle size
    • Crosslink density
    • Monomers and comonomers incorporated into formulation
  • Physical characteristics
    • Elasticity can be modified to change the rate of modulus with stress.
    • Modulus can be modified to mimic specific adipose tissue.
  • Gel aggregates on contact with normal serum with no migration into lymphatic tissue.
  • Potential to seal slow leak at site with no further material release.

Viscous Gel Physical Properties Elastic Modulus

Viscous Gel Physical Properties Deflection  

  • Increasing polymer weight percent in gel increases resistance to deflection.
  • Increasing HPMA percent composition increases resistance to deflection.
  • Deflection is nonlinear but this is consistent with elastic gel materials