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

Abid, Zarmeena; Strindberg, Sophie; Javed, Madeeha M.; Mazzoni, Chiara; Vaut, Lukas; Nielsen, Line Hagner; Gundlach, Carsten; Petersen, Ritika Singh; Müllertz, Anette; Boisen, Anja; Keller, Stephan Sylvest

doi:10.1039/c9lc00527g

Cited by 28 publications

(46 citation statements)

References 40 publications

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“…While the ex vivo intestinal permeation studies showed the potential of unidirectional release for permeation enhancement across intestinal tissue, this effect was not observed in vivo. Fluorescent microscopic examination of the stomachs and small intestines of the rats after the in vivo study revealed that all MCs had undergone complete transit from ileum to caecum after 4 h, which is consistent with another recent study of biodegradable MCs [31]. Previous studies have shown SU-8 MCs embedded in the intestinal mucus in in situ intestinal perfusion studies [18].…”

Section: In Vivo Studiessupporting

confidence: 87%

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

Jørgensen

Venkatasubramanian

et al. 2020

Pharmaceutics

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Enhancing the oral bioavailability of peptides has received a lot of attention for decades but remains challenging, partly due to low intestinal membrane permeability. Combining a permeation enhancer (PE) with unidirectionally releasing microcontainers (MCs) has previously been shown to increase insulin permeation across Caco-2 cell monolayers. In the present work, this setup was further employed to compare three common PEs—sodium caprate (C10), sodium dodecyl sulfate (SDS), and lauroyl carnitine. The concept was also studied using porcine intestinal tissue with the inclusion of 70 kDa fluorescein isothiocyanate-dextran (FD70) as a pathogen marker. Moreover, a combined proteolysis and Caco-2 cell permeation setup was developed to investigate the effect of soybean trypsin inhibitor (STI) in the MCs. Lastly, in vivo performance of the MCs was tested in an oral gavage study in rats by monitoring blood glucose and insulin absorption. SDS proved to be the most potent PE without increasing the ex vivo uptake of FD70, while the implementation of STI further improved insulin permeation in the combined proteolysis Caco-2 cell setup. However, no insulin absorption in rats was observed upon oral gavage of MCs loaded with insulin, PE and STI. Post-mortem microscopic examination of their gastrointestinal tract indicated lack of intestinal retention and optimal orientation by the MCs, possibly precluding the potential advantage of unidirectional release.

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Section: In Vivo Studiessupporting

confidence: 87%

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

Jørgensen

Venkatasubramanian

et al. 2020

Pharmaceutics

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“…Microcontainers in the biodegradable polymer PCL were fabricated by a hot punching process as previously described (Abid et al, 2019;Petersen et al, 2015). These microcontainers were fabricated on a water soluble PVA substrate containing 1,600 microcontainers.…”

Section: Fabrication Of Su-8 and Pcl Microcontainersmentioning

confidence: 99%

Ex vivo intestinal perfusion model for investigating mucoadhesion of microcontainers

Mosgaard

Strindberg

Abid

et al. 2019

International Journal of Pharmaceutics

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“…[31][32][33]. Recently, microcontainers were developed in poly-Ɛcaprolactone (PCL) in order to have a biodegradable oral drug delivery device in microscale [34]. In a pharmacokinetic study in rats, the PCL microcontainers revealed trends towards a higher AUC when compared to paracetamol in coated gelatin capsules (60 ± 33 and 39 ± 18 μg min ml −1 , respectively).…”

Section: Passive Microdevices For Oral Drug Delivery: Opportunities Amentioning

confidence: 99%

Orally ingestible medical devices for gut engineering

Mandsberg

Christfort

Kamguyan

et al. 2020

Advanced Drug Delivery Reviews

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Orally ingestible medical devices provide significant advancement for diagnosis and treatment of gastrointestinal (GI) tract-related conditions. From micro-to macroscale devices, with designs ranging from very simple to complex, these medical devices can be used for site-directed drug delivery in the GI tract, real-time imaging and sensing of gut biomarkers. Equipped with uni-direction release, or self-propulsion, or origami design, these microdevices are breaking the barriers associated with drug delivery, including biologics, across the GI tract. Further, on-board microelectronics allow imaging and sensing of gut tissue and biomarkers, providing a more comprehensive understanding of underlying pathophysiological conditions. We provide an overview of recent advances in orally ingestible medical devices towards drug delivery, imaging and sensing. Challenges associated with gut microenvironment, together with various activation/actuation modalities of medical devices for micromanipulation of the gut are discussed. We have critically examined the relationship between materials-device design-pharmacological responses with respect to existing regulatory guidelines and provided a clear roadmap for the future.

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

Abstract: We demonstrate the first complete study on fabrication of biodegradable microcontainers including their evaluation in vitro and in vivo.

Cited by 28 publications

References 40 publications

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

In Vitro, Ex Vivo and In Vivo Evaluation of Microcontainers for Oral Delivery of Insulin

Ex vivo intestinal perfusion model for investigating mucoadhesion of microcontainers

Orally ingestible medical devices for gut engineering

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