Nanoengineered Surfaces Enhance Drug Loading and Adhesion

Abstract

To circumvent the barriers encountered by macromolecules at the gastrointestinal mucosa, sufficient therapeutic must be delivered in close proximity to cells 1 . Previously, we have shown that silicon nanowires penetrate the mucous layer and adhere directly to cells under high shear 2 . In this work, we characterize potential reservoirs and load macromolecules into space created between nanowires. We show significant increases in loading capacity due to nanowires while retaining adhesion of loaded particles under high shear. KeywordsNanowires; adhesion; drug delivery; hierarchical nanostructures Mucosal tissues, such as those lining the oral cavity and gastrointestinal tract, have great potential for delivery of therapeutic macromolecules, but drug absorption is often thwarted by chemical and physical barriers. The epithelia is covered in a 1-50 μm motile mucus gel layer with pores of roughly 100 nm [3][4][5] . Like chyme, which clears the entire small intestine within 150 to 240 minutes 6, 7 , the mucus layer turns over every 50-170 minutes 8 . As a result of the viscosity and motility of the mucus, therapeutic macromolecules take longer to diffuse to cells, increasing their susceptibility to degradation and removal 1 .Adhesion and encapsulation technologies have been developed to combat the harsh gastrointestinal environment. Increased residence time in the upper small intestine and adhesion in close proximity or directly to cells increases the local concentration gradient at the epithelial layer, promoting transport 9-11 . Encapsulation in polymers, microparticles, or nanoparticles can protect therapeutics from degradation, ensuring that they remain active until they are released near the tissue.Numerous adhesives have been developed with the intent of increasing microparticle gastrointestinal residence time. However, most chemical adhesives function through mucoadhesion, primarily attaching to the mucus layer on top of the tissue, and thus being * Additional contact information for Tejal A. Desai: Tejal.Desai@ucsf.edu, phone -415-514-4503, fax -415-476-2414. Supporting Information Available: Further descriptions of the methods used in this paper, as well as theoretical surface area and geometry calculations and discussion, elution curves, and a consideration of loading capacity and therapeutic efficacy are available in the Supporting Information section. This material is available free of charge via the Internet at http://pubs.acs.org. 14,15 , and may lead to potentially toxic accumulations in the liver, kidneys, and spleen 16,17 . Microparticles can be fabricated with hollow reservoirs or engineered pores using photolithography, etching, or anodization 9, 18 . Although these technologies significantly improve loading capacity compared to nanoparticles, the additional fabrication complexity considerably increases the overall cost of the devices, and the larger size reduces diffusion through the mucus layer. NIH Public AccessWe have shown that integrating the diffusive properties at the nanoscale,...

Micro/nanofabricated platforms for oral drug delivery

“…Several researchers have fabricated nanowire-coated oral microdevices and used the high surface area of nanowires to effectively load both aqueous and non-aqueous drugs via capillary action. After solvent evaporation, the drug crystallizes over the microdevice surface at the base of the nanowires (Figure 4 D) [71, 72, 74]. Because solvents of drug solutions can evaporate in a manner of minutes with >90% of drug collecting over nanowire-coated microdevices [74], loading via capillary action is efficient in both throughput and minimizing drug waste.…”

Entering the Era of Nanoscience: Time to Be So Small Vuk Uskokovíc

“…14). These composite particles effectively adhered to microvilli of the epithelial cells of the gastrointestinal tract, 90,91 prolonging the drug retention time and promoting the paracellular transport of small and medium sized drug molecules across the epithelium (Fig. 15).…”

Nanostructured Materials for Ocular delivery: Nanodesign for Enhanced bioadhesion, Transepithelial Permeability and Sustained Delivery

“…Using this approach, researchers have used nanostructured microparticles for increased retention time in oral drug delivery applications. For example, in vitro studies have shown that nanoengineered microparticles, fabricated by growth of silicon nanowires on the surface of glass microbeads, are able to achieve significantly enhanced bioadhesion to a layer of intestinal epithelial (Caco-2) cells in the presence of flow compared with bare microparticles [21,24,25]. …”