In Vitro Digestion and Gut Microbiota Fermentation of the Anticancer Marine Drug BG136: Stability and Biotransformation Investigation

• Published in: Marine drugs Vol. 23; no. 4; p. 156
• Main Authors: Li, Xintong, Xu, Shuying, Chen, Baiyuan, Gao, Pengcheng, Lv, Youjing, Shang, Qingsen, Yu, Guangli, Li, Guoyun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.04.2025; MDPI
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic drugs; BG136; Bioavailability; Biological Availability; Biopharmaceutics; Biotransformation; Cancer; Carbohydrates; Care and treatment; Chemical properties; Chromatography; Clinical trials; Digestion; Digestive system; Drug delivery systems; Drug development; Drug therapy; Drugs; Enzymes; Fatty acids; Fatty Acids, Volatile - metabolism; Fermentation; Gastrointestinal Microbiome - drug effects; Gastrointestinal system; Gastrointestinal tract; Glucan; Gut microbiota; Humans; Intestinal microflora; Metabolism; Metabolites; Microbial flora; Microbiota; Microorganisms; Molecular weight; Oligosaccharides; Oral administration; Pharmaceutical research; Pharmacokinetics; Physiological aspects; Prebiotics; Propionic acid; SCFAs; Stability; Structural integrity; China; digestion; SCFAs; fermentation; BG136; gut microbiota
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md23040156

BG136, a β-1,3/1,6-glucan derived from Durvillaea antarctica, is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a pivotal focus for our future drug development research; therefore, elucidating the gastrointestinal fate of BG136 becomes imperative. This study investigated the stability and biotransformation of BG136 via in vitro digestion and gut microbiota fermentation. The results confirmed BG136’s structural integrity, resistance to degradation in a highly acid environment and by gastrointestinal tract enzymes. In contrast, BG136 was degraded by intestinal bacteria into mid-size fragments along with smaller oligosaccharides. Additionally, the biotransformation process notably elevated total short-chain fatty acids (SCFAs) to 38.37 ± 3.29 mM, representing a 59.4% increase versus controls (24.08 ± 2.29 mM), with propionic acid exhibiting the most substantial increase. Meanwhile, the process was accompanied by significant microbial regulation, including an increase in beneficial genera (Lactobacillus, Enterococcus) and a reduction in Lachnoclostridium populations. Overall, these findings systematically map the oral bioavailability challenges and prebiotic potential of BG136, highlighting its microbiota-modulating capacity through species-specific ecological regulation, providing insights into oral drug development for BG136.