Microfabrication of an asymmetric, multi-layered microdevice for controlled release of orally delivered therapeutics

Abstract

SummaryThe creation of an oral drug delivery platform to administer chemotherapeutic agents effectively can not only increase patient compliance, but also potentially diminish drug toxicity. A microfabricated device offers advantages over conventional drug delivery technology. Here we describe the development of a multi-layered polymeric drug-loaded microfabricated device (microdevice) for the oral delivery of therapeutics, which offers unidirectional release of multiple therapeutics. The imaging and release of therapeutics from the multi-layered device was performed with three different fluorescently labeled albumins. The release of insulin and chemotherapeutic camptothecin was also observed to be released in a controlled manner over the course of 180 minutes in vitro. Furthermore, asymmetric delivery was shown to concrete drug at the device/cell interface, wherein 10 times more drug permeated an intestinal epithelial cell monolayer, compared to unprotected drug-loaded hydrogels. The bioactivity of the released chemotherapeutic was shown with cytostasis of colorectal adenocarcinoma cells. Cytostasis of drug loaded hydrogels was significantly higher than control empty hydrogel laden microdevices. Our results conclude that microfabrication of a hydrogel laden microdevice leads to a viable oral delivery platform for chemotherapeutics.

Microtechnologies for Drug Delivery

“…Microfabrication allows for design control and drug elution. For example, an asymmetric [ 26,[87][88][89][90] . In addition, pore size can be micromachined from silicon to allow for single molecule release of drug, permitting zero-order kinetics ( Fig.…”

“…The Desai laboratory has designed an oral delivery vehicle that incorporates many of these features (Fig. 18.1 ) [ 26,27,[87][88][89][90][97][98][99][100] . These devices were initially developed in silicon through micromachining techniques [ 100 ] .…”

“…Building on the multi-layered device, a bi-polymeric device can be formulated with photolithography. Poly (ethylene glycol) dimethacrylate (PEGMA) has been incorporated into SU-8 microdevices for oral delivery of chemotherapeutics [ 88 ] ( Fig. 18.1 ).…”

Microfabricated implants for applications in therapeutic delivery, tissue engineering, and biosensing

“…(Supplementary Figure 1) Building on the multi-layered device, a bi-polymeric device can be formulated with photolithography. Poly (ethylene glycol) dimethacrylate (PEGMA) has been incorporated into SU-8 microdevices for oral delivery of chemotherapeutics 95. (Fig.…”

Planar Bioadhesive Microdevices: A New Technology for Oral Drug Delivery

“…Poly(methyl methacrylate) (PMMA), an FDA-approved polymeric material [47] used in contact lenses and bone cement and also known to be stable at low pH values [26], has been utilized in numerous oral microdevice designs [34–35, 48–51]. Microdevices have also been fabricated from SU-8, an epoxy-based negative photoresist originally developed as an ultra-thick photoresist [36, 52]. While SU-8 is not currently FDA approved, studies have shown that SU-8 is non-toxic as an implantable material [53–55].…”