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

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 imp...

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Published inMarine 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
LanguageEnglish
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
Online AccessGet full text
ISSN1660-3397
1660-3397
DOI10.3390/md23040156

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Abstract 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.
AbstractList 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.
BG136, a β-1,3/1,6-glucan derived from , 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 ( , ) and a reduction in 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.
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.
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.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.
Audience Academic
Author Li, Xintong
Shang, Qingsen
Xu, Shuying
Li, Guoyun
Lv, Youjing
Chen, Baiyuan
Gao, Pengcheng
Yu, Guangli
AuthorAffiliation 1 Key Laboratory of Marine Drugs, Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; lixintong20000723@163.com (X.L.); 17syxu@alumni.stu.edu.cn (S.X.); cbyngu@163.com (B.C.); gaopengchengsir@163.com (P.G.); 2015315@ouc.edu.cn (Y.L.); shangqingsen@ouc.edu.cn (Q.S.)
2 Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
AuthorAffiliation_xml – name: 2 Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China
– name: 1 Key Laboratory of Marine Drugs, Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; lixintong20000723@163.com (X.L.); 17syxu@alumni.stu.edu.cn (S.X.); cbyngu@163.com (B.C.); gaopengchengsir@163.com (P.G.); 2015315@ouc.edu.cn (Y.L.); shangqingsen@ouc.edu.cn (Q.S.)
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fermentation
BG136
gut microbiota
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Snippet 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...
BG136, a β-1,3/1,6-glucan derived from , is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a...
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...
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...
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StartPage 156
SubjectTerms 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
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Title In Vitro Digestion and Gut Microbiota Fermentation of the Anticancer Marine Drug BG136: Stability and Biotransformation Investigation
URI https://www.ncbi.nlm.nih.gov/pubmed/40278277
https://www.proquest.com/docview/3194622601
https://www.proquest.com/docview/3194656309
https://pubmed.ncbi.nlm.nih.gov/PMC12028602
https://doaj.org/article/f44029c833cb43db8d56df75d418ab7b
Volume 23
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