Environmental Science & Engineering, University of Texas at El Paso, El Paso, TX, 79965, USA.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Texas at El Paso, 1101 N. Campbell St, El Paso, TX, 79902, USA.
Cancer Metastasis Rev. 2023 Sep;42(3):699-724. doi: 10.1007/s10555-023-10099-x. Epub 2023 Mar 27.
Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.
癌症是全球主要的健康关注点，目前仍在不断寻求有效的治疗方法。自 RNAi 的发现及其作用机制被揭示以来，它已在针对各种疾病（包括癌症）的靶向治疗中显示出了潜力。RNAi 选择性沉默致癌基因的能力使它们成为癌症治疗的理想选择。由于患者的依从性和便利性，口服给药是药物给药的理想途径。然而，例如，口服给予的 RNAi（如 siRNA）必须穿过各种细胞外和细胞内的生物屏障才能到达作用部位。保持 siRNA 的稳定性直到它们到达靶向部位是非常具有挑战性和重要的。恶劣的 pH 值、厚厚的黏液层和核酸酶会阻止 siRNA 通过肠壁扩散，从而诱导治疗效果。进入细胞后，siRNA 会受到溶酶体的降解。多年来，人们已经考虑了各种方法来克服这些口服 RNAi 递送的挑战。因此，了解这些挑战和最新进展对于提供口服 RNAi 递送的新方法和先进方法至关重要。在此，我们总结了用于口服递送 RNAi 的递送策略以及最近在临床前阶段的进展。
