Crispino R, Lagreca E, Procopio A, D'Auria R, Corrado B, La Manna S, Onesto V, Di Natale C
Center for Advanced Biomaterials for Health Care (CABHC), Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, Napoli, Italy.
Department of Chemical Materials and Industrial Production (DICMaPI), University of Naples Federico II, P.le Tecchio 80, Naples 80125, Italy.
Soft Matter. 2025 Jan 29;21(5):792-818. doi: 10.1039/d4sm01222d.
In recent years, nano and micro drug delivery systems targeting the colon have gained more attention due to increasing interest in treating colon diseases such as colorectal cancer and inflammatory bowel disease, , Crohn's disease and ulcerative colitis. Usually, nanocarriers are exploited for their enhanced permeability properties, allowing higher penetration effects and bioavailability, while microcarriers are primarily used for localized and sustained release. In bowel diseases, carriers must go into a delicate environment with a strict balance of gut bacteria (, colon), and natural or biodegradable polymers capable of ensuring lower toxicity are preferred. However, these systems are primarily delivered orally, so the carrier must go through the whole gastrointestinal tract, where it encounters significant pH fluctuations, different mucus layers, several enzymes, and a long transit time. For this reason, various approaches have been explored and evaluated, especially using pH-responsive and time-dependent systems. This review provides an overview of the contemporary methodologies employed in orally administered nano- and microparticles for colon delivery, encompassing both and investigations. It evaluates their strengths, weaknesses, constraints, and potential enhancements, leveraging mathematical and microfluidic models. Furthermore, it focuses explicitly on systems that have already reached the market and are presently employed in treating severe colon diseases.
近年来，由于人们对治疗结肠疾病（如结直肠癌和炎症性肠病，包括克罗恩病和溃疡性结肠炎）的兴趣日益浓厚，靶向结肠的纳米和微米级药物递送系统受到了更多关注。通常，纳米载体因其增强的渗透性而被利用，从而实现更高的渗透效果和生物利用度，而微载体主要用于局部和持续释放。在肠道疾病中，载体必须进入肠道细菌（如结肠）平衡严格的微妙环境，因此优先选择能够确保较低毒性的天然或可生物降解聚合物。然而，这些系统主要通过口服给药，所以载体必须经过整个胃肠道，在此过程中会遇到显著的pH值波动、不同的黏液层、多种酶以及较长的转运时间。因此，人们探索并评估了各种方法，特别是使用pH响应和时间依赖性系统。本综述概述了用于结肠递送的口服纳米和微粒的当代方法，包括体内和体外研究。它利用数学和微流控模型评估了它们的优点、缺点、限制和潜在改进。此外，它明确关注已进入市场并目前用于治疗严重结肠疾病的系统。
