EFFECT OF SIZE, SURFACE-CHARGE, AND HYDROPHOBICITY ON THE TRANSLOCATION OF POLYSTYRENE MICROSPHERES THROUGH GASTROINTESTINAL MUCIN

Microspheres (MS) have been proposed for use as oral vaccine delivery vehicles (VDV); however, due to poor and variable absorption their cli nical utility is limited. The effects of size, zeta-potential, and sur face hydrophobicity on the translocation (P-T) permeabilities of polys tyrene (PS) MS with varying surface functional groups (amidine, carbox yl, carboxylate-modified [CML], and sulfate) were determined through g astrointestinal (GI) mucin. P-T were determined, under steady-state co nditions, using a modified Ussing-type diffusion chamber and a mucin p acket developed for use with the Transwell-Snapwell system. P-T follow ed the Stokes-Einstein relationship, demonstrating the limited ability of larger MS (>0.5 mu m) to diffuse through the mucin layer. P-T also varied according to the surface characteristics. Even though the zeta -potential did not correlate with the transport of MS through mucin, s urface ionization appears to be important in MS translocation. The PS- amidine MS were significantly less hydrophobic and had a higher P-T th an that of the other MS, suggesting that hydrophobicity is also a sign ificant factor in MS transport through mucin. While these results sugg est that mucin may be a significant barrier to the oral absorption of vaccines and VDVs in vivo, the rate-limiting barrier for the absorptio n of MS will be the intestinal mucosa. (C) 1997 John Wiley & Sons, Inc .