Session: POLY/PMSE Poster Session:

Mucosal delivery across the gastrointestinal tract, airway, and buccal epithelium is an attractive mode of therapeutic administration, but the challenge is to overcome mucus- and epithelial barriers. Degradable star polypept(o)ides can permeat both barriers and they are promising biomaterials for mucosal delivery. Star polypept(o)ides were obtained by initiation of benzyl-L-glutamate N-carboxyanhydride (NCA) from an 8-arm polypropylene dendrimer, with subsequent chain extension with sarcosine NCA. The hydrophobic poly(benzyl-L-glutamate) block length was maintained at 20 monomers, while the length of the hydrophilic poly(sarcosine) block ranged from 20 - 640 monomers to produce star polypept(o)ides with increasing hydrophilic : hydrophobic ratios. Transmision Electron Microscopy (TEM) images revealed elongated particles of ~120 nm length, while Dynamic Light Scattering (DLS) provides evidence of a decrease in the size of polymer aggregates in water with increasing poly(sarcosine) block length, with the smallest size obtained for the star PBLG₂₀-b-PSar₆₄₀. Fluorescein isothiocyanate (FITC)-conjugated PBLG₂₀-b-PSar₆₄₀ permeated artificial mucus and isolated rat mucus, as well as rat intestinal jejunal tissue mounted in Franz diffusion cells. A permeability coefficient (P_app) of 15.4 ± 3.1 x 10 ^-6cm/sec for FITC-PBLG₂₀-b-PSar₆₄₀ was calculated from the flux obtained with apical-side addition of 7.5 mg polypept(o)ide to jejunal tissue. The P_app could not be accounted for by flux of unconjugated FITC. Exposure to trypsin demonstrated enzymatic stability of FITC labeled polypept(o)ide over 2 h, but enzymatic degradation at the mucus-epithelial interface or during flux cannot be ruled out as contributing to the increased P_app. The absence of any histological damage to the jejunal tissue during the 2 h exposure suggests that flux was not associated with toxicity.

Andreas Heise

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