Korel Anastasia, Samokhin Alexander, Zemlyakova Ekaterina, Pestov Alexander, Blinova Elena, Zelikman Maxim, Tkachenko Vadim, Bets Viktoria, Kretien Svetlana, Arzhanova Elena, Litvinova Ekaterina
Faculty of Physical Engineering, Novosibirsk State Technical University, 630073 Novosibirsk, Russia.
Institute of Organic Synthesis n.a. I. Ya. Postovsky UB RAS, 620137 Ekaterinburg, Russia.
Gels. 2023 Sep 16;9(9):756. doi: 10.3390/gels9090756.
To date, few publications describe CEC's properties and possible applications-thus, further evaluation of these properties is a point of interest. The present in vitro model study aimed to evaluate a carboxyethylchitosan (CEC) gel with a degree of substitution of 1, cross-linked with glutaraldehyde at a polymer:aldehyde molar ratio of 10:1, as a potential carrier for delivering bacteriophages to various pH-fixed media (acidic, alkaline), and including gastrointestinal tract (GIT) variable medium. A quantitative analysis of bacteriophages released from the gel was performed using photon correlation spectrophotometry, and phage activity after emission into medium was evaluated using the spot test. The results showed that the CEC gel's maximum swelling ratios were at a nearly neutral alkaline pH. Increasing temperature enhances the swelling ratio of the gel independent from pH, up to 1127% at 37 °C and alkaline pH. The UV and photon correlation spectrophotometry showed equal gel release kinetics in both fixed media with acidic (pH = 2.2) and alkaline (pH = 7.4) pH environments at 37 °C, with the maximum release within two hours. However, phage lytic activity in the spot test during this simulation was absent. At the same time, we obtained an opaque phage lytic activity in the alkaline pH-fixed medium for at least three hours. Phages released from the tested CEC gel in different pHs suggest that this gel could be used for applications that require fast release at the treatment site both in acidic and alkaline pH. Such treatment sites could be a wound or even soil with mild acidic or alkaline pH. However, such CEC gel is not suitable as a delivery system to the GIT because of possible transported acid-sensitive agent (such as phages) release and destruction already in the stomach.
迄今为止,很少有出版物描述羧乙基壳聚糖(CEC)的特性及其可能的应用——因此,对这些特性的进一步评估是一个值得关注的问题。本体外模型研究旨在评估一种取代度为1、与戊二醛以聚合物:醛摩尔比10:1交联的羧乙基壳聚糖(CEC)凝胶,作为将噬菌体递送至各种pH固定介质(酸性、碱性)以及包括胃肠道(GIT)可变介质的潜在载体。使用光子相关分光光度法对从凝胶中释放的噬菌体进行定量分析,并使用斑点试验评估释放到介质中的噬菌体活性。结果表明,CEC凝胶的最大溶胀率出现在近中性碱性pH值下。温度升高会提高凝胶的溶胀率,且与pH无关,在37°C和碱性pH条件下最高可达1127%。紫外和光子相关分光光度法显示,在37°C时,该凝胶在酸性(pH = 2.2)和碱性(pH = 7.4)pH环境的两种固定介质中的释放动力学相同,在两小时内达到最大释放量。然而,在此模拟过程中,斑点试验中没有噬菌体裂解活性。同时,我们在碱性pH固定介质中至少三小时获得了不透明的噬菌体裂解活性。从测试的CEC凝胶在不同pH值下释放的噬菌体表明,这种凝胶可用于在酸性和碱性pH值的治疗部位都需要快速释放的应用。这样的治疗部位可以是伤口,甚至是pH值为轻度酸性或碱性的土壤。然而,这种CEC凝胶不适合作为向胃肠道的递送系统,因为可能在胃中就已经释放并破坏对酸敏感的药物(如噬菌体)。