PhD defence by Carmen Guimera

On Thursday 23 May 2024, Carmen Guimera defends her PhD thesis “Fabrication and in vitro in vivo evaluation of small polymeric devices for oral drug delivery”.

Time: 12:30

Place: Bldg. 341, aud. 23 & Zoom: https://dtudk.zoom.us/meeting/register/u5Aoce2oqj0qG9FLLRIrqHxvEqhh9warjHlY
Please be aware that the PhD defense may be recorded - This will also be informed at the beginning of the PhD defense.

Principal supervisor: Professor Anja Boisen
Co-supervisor: Senior Consultant Lasse Thamdrup
Co-supervisor: Senior Consultant Mahdi Ghavami

Members of assessment committee:
Professor Stephan S. Keller, DTU Nanolab
Professor David Brayden, University College Dublin
Professor Jürgen Siepmann, University of Lile

Chairperson:
Associate Professor, Fatemeh Ajalloueian, DTU Health Tech

Abstract:
The oral route is the preferred approach for systemic treatment and preventions of disease conditions. However, evolution has shaped our gut for the digestion of food and protection from foreign compounds. This leads to the presence of obstacles such as pH variations, enzymes and continuous generating mucus barriers covering the inner surface, which challenges the oral delivery of certain drugs. Engineered ingestible devices have been proposed to overcome these obstacles by protecting the drug compound and closely interacting with gastrointestinal (GI) wall during its release. This includes mucusembedding microcontainers, which interact via mucoadhesive forces, and mucus-penetrating selfunfolding foils (SUFs), which employ mechanical forces.

The aim of this PhD project is to assess the potential of these platforms to increase the drug absorption, as well as to investigate methodologies for their production. In this project, microcontainers with dual-compartments have been presented for sequential delivery of two compounds in vitro and in vivo, which can be relevant for the co-delivery of drugs and excipients that promote the absorption. To scale up the production of microcontainers in biodegradable materials, a novel scalable approach based on ultrasonic spray coating and microcutting is presented. Biodegradable microcontainers were developed for targeted immediate and enteric drug release, which was confirmed in vitro and in vivo. An enhanced drug absorption was observed compared to conventional powder suspensions. Finally, SUFs comprising flexible pH-sensitive polymers revealed successful in vitro encapsulation of a model drug until targeted release in the small intestine, which could be relevant for the oral delivery of macromolecules.

In conclusion, this thesis highlights the potential of mucus-embedding and mucus-penetrating devices as a future strategy in oral drug delivery. This could be useful for the delivery of drug compounds that are commonly delivered by other routes such as injections. Especially, if the presented platforms are intended to achieve an increased proximity and retention time in the GI epithelium.