Hot punching for loading of biodegradable microcontainers with budesonide-Soluplus film.

Micro-reservoir based drug delivery systems have the potential to provide targeted drug release locally in the intestine, i.e. at the inflamed areas of the intestine of patients with inflammatory bowel disease (IBD). In this study, microcontainers with a diameter of 300 µm and a height of 100 µm, asymmetrical geometry and the possibility to provide unidirectional release, are fabricated in the biodegradable polymer poly-ɛ-caprolactone (PCL) using hot punching. As a first step towards local treatment of IBD, a novel method for loading of microcontainers with the corticosteroid budesonide is developed. For this purpose, a budesonide-Soluplus drug-polymer film is prepared by spin coating and loaded into the microcontainer reservoirs using hot punching. The processing parameters are optimized to achieve a complete loading of a large number of containers in a single step. A poly(lactic-co-glycolic acid) (PLGA) 50:50 lid is subsequently applied by spray coating. Solid-state characterization indicates that the drug is in an amorphous state in the drug-polymer films and the in vitro drug release profile showed a 68% release over 10 h. The results demonstrate that hot punching can be employed both as a production and loading method for PCL microcontainers with the perspective of local treatment of IBD.

Investigation of Mucoadhesion and Degradation of PCL and PLGA Microcontainers for Oral Drug Delivery.

Microfabricated devices have been introduced as a promising approach to overcome some of the challenges related to oral administration of drugs and, thereby, improve their oral bioavailability. In this study, we fabricate biodegradable microcontainers with different polymers, namely poly-ɛ-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) 50:50 and PLGA 75:25 by hot punching. The mucoadhesion of the microcontainers is assessed with an ex vivo retention model on porcine intestinal tissue. Finally, in vitro degradation studies of the biodegradable microcontainers are completed for six weeks in simulated intestinal medium with the addition of pancreatic enzymes. Through SEM inspection, the PLGA 50:50 microcontainers show the first signs of degradation already after two weeks and complete degradation within four weeks, while the other polymers slowly degrade in the medium over several weeks.

Ex vivo intestinal perfusion model for investigating mucoadhesion of microcontainers.

Micro fabricated delivery systems have shown promise in increasing oral bioavailability of drugs. Micrometer-sized polymeric devices (microcontainers) have the potential to facilitate unidirectional drug release directly into the intestinal mucosa whereby, drug absorption can be enhanced. The aim of this study was to develop an ex vivo model to investigate mucosal adhesion and orientation of microcontainers. Furthermore, to investigate how microcontainers with varying height, shape and material behave in regards to mucoadhesion and orientation. Microcontainers were placed at the top of an inclined piece of porcine small intestine. The tissue was perfused with biorelevant medium followed by microscopic examination to observe the orientation and amount of microcontainers on the tissue. The mucoadhesion of the microcontainers were evaluated based on the observed position on the tissue after being exposed to flow. When comparing the varying types of microcontainers, good adhesion was in general observed since most of the microcontainers were located in the beginning of the intestine. Microcontainers fabricated from the epoxy-based photoresist SU-8 had a slightly better adherence than those fabricated from poly-ɛ-caprolactone (PCL). The orientation of the microcontainers appeare to be dictated mainly by the height. In general, the model showed promising results in evaluating mucoadhesion and orientation.

Biodegradable microcontainers - towards real life applications of microfabricated systems for oral drug delivery.

Microfabrication techniques have been applied to develop micron-scale devices for oral drug delivery with a high degree of control over size, shape and material composition. Recently, microcontainers have been introduced as a novel approach to obtain unidirectional release to avoid luminal drug loss, enhance drug permeation, protect drug payload from the harsh environment of the stomach, and explore the ability for targeted drug delivery. However, in order to eventually pave the way for real life applications of these microfabricated drug delivery systems, it is necessary to fabricate them in biodegradable materials approved for similar applications and with strategies that potentially allow for large scale production. In this study, we for the first time evaluate biodegradable microcontainers for oral drug delivery. Asymmetric poly-ε-caprolactone (PCL) microcontainers with a diameter of 300 µm and a volume of 2.7 nL are fabricated with a novel single-step fabrication process. The microcontainers are loaded with the model drug paracetamol and coated with an enteric pH-sensitive Eudragit® S100 coating to protect the drug until it reaches the desired location in the small intestine. In vitro dissolution studies are performed to assess the drug load and release profile of the PCL microcontainers. Finally, in vivo studies in rats showed a higher bioavailability compared to conventional dosage forms and confirm the potential of biodegradable microcontainers for oral drug delivery.