Nanoparticle technologies for drug delivery have attracted interest due to their beneficial physicochemical properties that can create opportunities to improve pharmacokinetics and toxicology profiles of existing molecules, for example by solubilising hydrophobic molecules and decreasing clearance. Macromolecules including peptides and proteins currently dominate development pipelines, however they are currently limited to injectable formats. Two problems prevent their oral delivery: (i) instability due to enzymatic degradation and (ii) low small intestinal epithelial permeability. Approaches to enable oral peptide delivery typically involve permeation – enhancers and/or nanotechnology. Here, we created a silica – based nanoparticle construct with loading capacity of human insulin which may be suitable for oral administration. The physicochemical properties of the nanoparticles were studied using dynamic light scattering, transmission electron microscopy, and zeta potential, HPLC and <sup>1</sup>H nuclear magnetic resonance were used to determine peptide association efficiency and protein content. The hydrodynamic diameter range was found to be 100 – 400 nm, with a relatively high loading capacity (≥ 40%), as measured by HPLC. The reproducibility of the synthesis was evident from a batch – to – batch variability in size and loading of ~10%. The retention of secondary structure of particle – released insulin was confirmed by circular dichroism (CD), while bioactivity was demonstrated in rats following sub – cutaneous administration of a 1 IU/kg dose. Finally, the particle released insulin increasingly more rapidly as the pH and salinity of the media was increased. Importantly dissolution occurred in the span of a several hours at pH 2.3, as is necessary for stability in the stomach. We are currently evaluating the silica – based particles potential for oral delivery in a rat model.

Insulin – containing silica nanoparticles with a high loading capacity and demonstration of bioactivity: Potential for oral delivery

256th National Meeting (2018)

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