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Mucoadhesive chitosan microcapsules for controlled gastrointestinal delivery and oral bioavailability enhancement of low molecular weight peptides

生物利用度 化学 壳聚糖 光老化 口服 抗氧化剂 体内 药理学 最大值 控制释放 药代动力学 生物化学 医学 生物技术 皮肤病科 生物
作者
Kyungjik Yang,Hwa Seung Han,Seung Hwan An,Kyung Hoon Park,Keonwook Nam,Shinha Hwang,Yuyeon Lee,Sung Yeon Cho,Taehyung Kim,Deokyeong Choe,Sang Won Kim,Wonkyu Yu,Hyun Ah Lee,Jiyong Park,SangGuan You,Dong‐Gyu Jo,Ki Young Choi,Young Hoon Roh,Jae Hyung Park
出处
期刊:Journal of Controlled Release [Elsevier BV]
卷期号:365: 422-434 被引量:12
标识
DOI:10.1016/j.jconrel.2023.10.021
摘要

A bioactive compound, collagen peptide (CP), is widely used for biological activities such as anti-photoaging and antioxidant effects, with increased oral bioavailability because of its low molecular weight and high hydrophilicity. However, controlling release time and increasing retention time in the digestive tract for a more convenient oral administration is still a challenge. We developed CP-loaded chitosan (CS) microcapsules via strong and rapid ionic gelation using a highly negative phytic acid (PA) crosslinker. The platform enhanced the oral bioavailability of CP with controlled gastrointestinal delivery by utilizing the mucoadhesiveness and tight junction-opening properties of CS. CS and CP concentrations varied from 1.5 to 3.5% and 0–30%, respectively, for optimal and stable microcapsule synthesis. The physicochemical properties, in vitro release profile with intestinal permeability, in vivo oral bioavailability, in vivo biodistribution, anti-photoaging effect, and antioxidant effect of optimized CS microcapsules were analyzed to investigate the impact of controlling parameters. The structure of CS microcapsules was tuned by PA diffused gradient ionic cross-linking degree, resulting in a controlled CP release region in the gastrointestinal tract. The optimized microcapsules increased Cmax, AUC, and tmax by 1.5-, 3.4-, and 8.0-fold, respectively. Furthermore, CP in microcapsules showed anti-photoaging effects by downregulating matrix metalloproteinases-1 via antioxidant effects. According to our knowledge, this is the first study to microencapsulate CP for oral bioavailability enhancement. The peptide delivery method employed is simple, economical, and can be applied to customize bioactive compound administration.
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