| The pharmaceutical and biotechnology industries are currently developing numerous peptides, proteins, biopolymer and macromolecular drugs for the treatment of a variety of diseases. However, many of these biological drug forms have poor bioavailability when administered orally due to degradation by proteolytic enzymes and loss of drug into the intestinal lumen. In order to overcome these disadvantages, increasing interest has been placed on advanced carrier systems for more efficient delivery.; In response, the aim of this work was to fabricate microparticulate patch-like systems containing cytoadhesive properties using novel off-wafer approaches to traditional MEMS-based techniques. The use of micro fabrication techniques allowed for precise control over size and shape. The size of the microdevices (0.0225 mm2) was designed small enough to have adequate contact with the intestinal wall while large enough to prevent endocytosis of the entire particle. The shape of the microfabricated devices was designed flat and thin to maximize contact area with the intestinal lining and minimize side areas exposed to the constant flow of liquids through the intestine. The devices were fabricated to incorporate single or multiple drug reservoirs to contain and protect a number of drugs/biomolecules of interest. In addition, the integration of supplementary features, such as microposts, was explored to enhance permeation of drug through the mucus layer and shed mucosa.; Accordingly, the following three aims were addressed: (1) polymeric microdevices were manufactured using traditional microfabrication techniques; (2) the device surface was chemically modified to incorporate cell-specific, lectin-mediated targeting mechanisms; (3) the interfacial effects of selective surface chemistry and architecture were determined utilizing in vitro models of the gastrointestinal tract. It was shown that these modified microdevices have improved cytoadhesive properties toward Caco-2 cell monolayers. Additionally, the modified microdevices remained anchored to the cells in comparison to the unstable attachment of microspheres. By examining transepithelial electrical resistance and diffusion of phenol red through the monolayer, the microdevices were found to be biocompatible and perhaps even beneficial for paracellular transport. |
