Abstract
While the oral drug delivery route has traditionally been the most popular among patients, it is estimated that 90% of therapeutic compounds possess oral bioavailability limitations. Thus, the development of novel drug carriers for more effective oral delivery of therapeutics is an important goal. Composite particles made by growing nanoscopic silicon wires from the surface of narrowly dispersed, microsized silica beads were previously shown to be able to (a) adhere well onto the epithelium by interdigitating their nanowires with the apical microvilli and (b) increase the permeability of Caco-2 cell monolayers with respect to small organic molecules in direct proportion to their concentration. A comparison between the effects of spherical and planar particle morphologies on the permeability of the epithelial cell layer in vitro and in vivo presented the subject of this study. Owing to their larger surface area, the planar particles exhibited a higher drug-loading efficiency than their spherical counterparts, while simultaneously increasing the transepithelial permeation of a moderately sized model drug, insulin. The insulin elution profile for planar nanowire-coated particles displayed a continual increase in the cumulative amount of the released drug, approaching a constant release rate for a 1-4 h period of the elution time. An immunohistochemical study confirmed the ability of planar silica particles coated with nanowires to loosen the tight junction of the epithelial cells to a greater extent than the spherical particles did, thus, enabling a more facile transport of the drug across the epithelium. Transepithelial permeability tests conducted for model drugs ranging in size from 0.4 to 150 kDa yielded three categories of molecules depending on their permeation propensities. Insulin belonged to the category of molecules deliverable across the epithelium only with the assistance of nanowire-coated particles. Other groups of drugs, smaller and bigger, respectively, either did not need the carrier to permeate the epithelium or were not able to cross it even with the support from the nanowire-coated particles. Bioavailability of insulin orally administered to rabbits was also found to be increased when delivered in conjunction with the nanowire-coated planar particles.