UCSF

Oral Drug Delivery

Oral dosing is preferred by both patients and providers because it is less invasive than injectables and leads to higher patient adherence. As the range of pharmaceutical products expands to include peptides, proteins, biopolymer, and macromolecular drugs, many compounds are poorly bioavailable when administered orally and often fail to be therapeutically effective. We have developed hierarchical nanoengineered microparticles, microdevices, and monodispersed polymeric particles to address these challenges and ensure that sensitive cargos are protected against degradation in the GI tract, and those therapeutics are delivered at the site where they will be the most effective. We are also interested in understanding how structural cues can influence bioadhesion and drug permeability at the epithelial interface.

Future Work: Assessing bioactivity of loaded protein and tracking device transit in vivo 

Recent Publications: Nemeth CL, Lykins WR, et al. (2019) Pharm Res

Point(s) of Contact: Eva Hansen, Will Lykins

Layer-by-layer Planar Microdevices for Oral Protein Delivery 

(A) Devices are fabricated, loaded, and capped in a bottom-up approach using a picoliter printer. (B) Devices are printed onto a silicon wafer (above), with representative SEM image of dispersed devices (below). (C) Different capping formulations of Eudragit polymers dictate the release of a model protein API (insulin) from devices in simulated intestinal fluid. Data represented as mean ± 1 SD, scale bars = 100 μm.

targeted attachment, enterocyte, microvilli, drug transport

Planar microdevices (left) can be used to release multiple drugs across the intestinal barrier.

unidirectional diffusion microdevices

Unidirectional diffusion microdevices a) loaded with three different fluorescent model drugs and b) coated with a fluorescent surface coating.

chart

The cumulative release behavior of three model drugs from one planar microdevice with three different hydrogel cross-linking concentrations.