Transdermal delivery of macromolecules using solid-state biodegradable microstructures.

Purpose: The purpose of this work is to demonstrate the feasibility of using a proprietary technology called MicroCor™, based on solid-state, biodegradable microstructures (SSBMS), for transdermal delivery of macromolecules.

Methods: The proteins FITC-BSA (66 kDa) and recombinant protective antigen (rPA; 83 kDa) were incorporated into SSBMS arrays using a mold-based, liquid formulation casting and drying process. Arrays were applied to the skin with a custom applicator and then inspected to assess the extent of microstructure dissolution.

Plasmid DNA and siRNA transfection of intestinal epithelial monolayers by electroporation.

This study was conducted to evaluate the ability of electroporation to efficiently transfect differentiated intestinal epithelial monolayers with plasmid DNA and to determine whether electroporation can transfect these monolayers with short-interfering RNA (siRNA) to cause gene silencing. Confluent T84 monolayers were transfected with reporter plasmids expressing luciferase or green-fluorescent protein or with siRNA directed against the nuclear envelope proteins lamin A/C using electroporation. Optimized electroporation conditions resulted in luciferase and GFP expression.

Increased permeability of intestinal epithelial monolayers mediated by electroporation.

This study assessed whether electroporation enhances transport across intact intestinal epithelial monolayers that mimic the intestinal epithelium. Confluent Caco-2 monolayers were exposed to electroporation pulses and then monitored over time for transepithelial transport of calcein, a small fluorescent tracer, or fluorescein-labeled bovine serum albumin, a large protein. Cumulative transport of both molecules across the monolayers increased significantly (up to 34-fold) after electroporation and depended on electroporation voltage and pulse length and on molecular size.

Electroporation-mediated delivery of molecules to model intestinal epithelia.

This study was conducted to determine if electroporation can deliver membrane-impermeant molecules intracellularly to intact, physiologically competent monolayers that mimic the intestinal epithelium. In addition, the long-term effects of electroporation on these monolayers were studied to determine the kinetics with which monolayers recover barrier function. Caco-2 and T84 cells were electroporated as monolayers using calcein and fluorescein-labeled bovine serum albumin as marker molecules for measuring delivery into cells.