Colon-Targeted Delivery of IgY Against Clostridium difficile Toxin A and B by Encapsulation in Chitosan-Ca Pectinate Microbeads.
This study investigated the use of a newly developed chitosan-Ca pectinate microbead formulation for the colon-targeted delivery of anti-A/B toxin immunoglobulin of egg yolk (IgY) to inhibit toxin binding to colon mucosa cells. The effect of the three components (pectinate, calcium chloride, and chitosan) used for the microbead production was examined with the aim of identifying the optimal levels to improve drug encapsulation efficiency, swelling ratio, and cumulative IgY release rate. The optimized IgY-loaded bead component was pectin 5% (w/v), CaCl23% (w/v), and chitosan 0.5% (w/v). Formulated beads were spherical with 1.2-mm diameter, and the drug loading was 45%. An in vitro release study revealed that chitosan-Ca pectinate microbeads inhibited IgY release in the upper gastrointestinal tract and significantly improved the site-specific release of IgY in the colon. An in vivo rat study demonstrated that 72.6% of biologically active IgY was released specifically in the colon. These results demonstrated that anti-A/B toxin IgY-loaded chitosan-Ca pectinate oral microbeads improved IgY release behavior in vivo, which could be used as an effective oral delivery platform for the biological treatment of Clostridium difficile infection (CDI).
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China.
Pingping
P
Xing
School of Pharmaceutical Sciences, Shandong Binzhou Medical University, Yantai, 264003, China.
Yanan
Y
Shi
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Chuangchuang
C
Dong
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Hong
H
Liu
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Yan
Y
Cheng
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Junbo
J
Sun
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Dalei
D
Li
Shandong Luye Pharmaceutical Company, Yantai, 264003, China.
Min
M
Li
School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Yantai University, Yantai, 264005, China. sunkx@ytu.edu.cn.
Kaoxiang
K
Sun
Shandong Luye Pharmaceutical Company, Yantai, 264003, China. fengdx@hotmail.com.|School of Pharmaceutical Sciences, Shandong Binzhou Medical University, Yantai, 264003, China. fengdx@hotmail.com.
Dongxiao
D
Feng
D000818:Animals; D000930:Antidiarrheals / Q000008:administration & dosage / Q000493:pharmacokinetics; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D003015:Clostridium Infections / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000382:microbiology; D016503:Drug Delivery Systems; D004768:Enterotoxins / Q000378:metabolism*; D007136:Immunoglobulins / Q000008:administration & dosage / Q000494:pharmacology; D008863:Microspheres; D010368:Pectins / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats
D000930:Antidiarrheals; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001672:Biocompatible Materials; D004768:Enterotoxins; C016512:IgY; D007136:Immunoglobulins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D010368:Pectins; D048271:Chitosan
Clostridium difficile; IgY; colonic-specific delivery; microbeads; pectin