pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions

Abdi，Fatma1; Buzhor，Marina Green1; Zellweger，Nadia1; Zhi-Luo，2; Leroux，Jean Christophe1

2024

10.1016/j.jconrel.2023.11.048

Journal of Controlled Release   影响因子和分区

0168-3659

1873-4995

Microbiome-based therapies hold great promise for treating various diseases, but the efficient delivery of live bacteria to the colon remains a challenge. Furthermore, current oral formulations, such as lyophilized bacterial capsules or tablets, are produced using processes that can decrease bacterial viability. Consequently, high dosages are required to achieve efficacy. Herein, we report the design of pressure-sensitive colonic capsules for the encapsulation and delivery of aqueous suspensions of live bacteria. The capsules consisted of 2 functional thin-films (hydrophobic and enteric) of ethyl cellulose and Eudragit S100 dip-coated onto hydroxypropyl methylcellulose molds. The capsules could be loaded with aqueous media and provide protection against acidic fluids and, to some extent, oxygen diffusion, suggesting their potential suitability for delivering anaerobic bacterial strains. Disintegration and mechanical studies indicated that the capsules could withstand transit through the stomach and upper/proximal small intestinal segments and rupture in the ileum/colon. In vitro studies showed that bacterial cells (anaerobic and aerobic commensals) remained highly viable (74–98%) after encapsulation and exposure to the simulated GI tract conditions. In vivo studies with a beagle dog model revealed that 67% of the capsules opened after 3.5 h, indicating content release in the distal gastrointestinal tract. These data demonstrate that live aqueous bacterial suspensions comprised of both aerobic and anaerobic commensals can be encapsulated and in the future might be efficiently delivered to the distal gastrointestinal tract, suggesting the practical applications of these capsules in microbiome-based therapies.

Aqueous suspensions Colonic delivery Live bacteria Microbiome Pressure capsules

SCI ; EI

英语

其他

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85178996282

Scopus

1.Institute of Pharmaceutical Sciences,Department of Chemistry and Applied Biosciences,ETH Zürich,Zürich,8093,Switzerland
2.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China

Abdi，Fatma,Buzhor，Marina Green,Zellweger，Nadia,et al. pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions[J]. Journal of Controlled Release,2024,365:688-702.

Abdi，Fatma,Buzhor，Marina Green,Zellweger，Nadia,Zhi-Luo，,&Leroux，Jean Christophe.(2024).pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions.Journal of Controlled Release,365,688-702.

Abdi，Fatma,et al."pH-dependent pressure-sensitive colonic capsules for the delivery of aqueous bacterial suspensions".Journal of Controlled Release 365(2024):688-702.