Abstract：
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.
摘要：
一种生物活性化合物,胶原蛋白肽（CP），广泛用于生物活性，例如抗光老化和抗氧化作用，由于其低分子量和高亲水性，增加了口服生物利用度。然而,为了更方便的口服给药，控制释放时间和增加在消化道中的保留时间仍然是一个挑战。我们使用高度负的植酸（PA）交联剂通过强且快速的离子凝胶化开发了负载CP的壳聚糖（CS）微胶囊。通过利用CS的粘膜粘附性和紧密连接开放特性，该平台通过受控的胃肠道递送提高了CP的口服生物利用度。CS和CP浓度从1.5到3.5%和0-30%不等，分别,最佳和稳定的微胶囊合成。物理化学性质，具有肠通透性的体外释放曲线，体内口服生物利用度，体内生物分布，抗光老化效果，并对优化后的CS微胶囊的抗氧化效果进行了分析,考察了控制参数的影响。通过PA扩散梯度离子交联度调节CS微胶囊的结构，在胃肠道中产生受控的CP释放区。优化的微胶囊增加了Cmax，AUC,tmax为1.5-，3.4-,8.0倍，分别。此外，微胶囊中的CP通过抗氧化作用下调基质金属蛋白酶-1表现出抗光老化作用。据我们所知,这是第一个将CP微囊化用于提高口服生物利用度的研究.所采用的肽递送方法是简单的,经济,并可用于定制生物活性化合物给药。
