Alrbyawi Hamad
Department of Pharmaceutics and Pharmaceutical Industries, College of Pharmacy, Taibah University, Madinah 41477, Saudi Arabia.
Pharmaceutics. 2024 Jul 22;16(7):966. doi: 10.3390/pharmaceutics16070966.
5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades to treat various types of cancer. It is considered the standard first-line treatment for patients with metastatic colorectal cancer. Unfortunately, traditional chemotherapy with 5-FU presents many limitations, such as a short half-life, a low bioavailability, and a high cytotoxicity, affecting both tumor tissue and healthy tissue. In order to overcome the drawbacks of 5-FU and enhance its therapeutic effectiveness against colorectal cancer, many studies have focused on designing new delivery systems to successfully deliver 5-FU to tumor sites. Liposomes have gained attention as a well-accepted nanocarrier for several chemotherapeutic agents. These amphipathic spherical vesicles consist of one or more phospholipid bilayers, showing promise for the drug delivery of both hydrophobic and hydrophilic components in addition to distinctive properties, such as biodegradability, biocompatibility, a low toxicity, and non-immunogenicity. Recent progress in liposomes has mainly focused on chemical and structural modifications to specifically target and activate therapeutic actions against cancer within the proximity of tumors. This review provides a comprehensive overview of both internal-stimuli-responsive liposomes, such as those activated by enzymes or pH, and external-stimuli-responsive liposomes, such as those activated by the application of a magnetic field, light, or temperature variations, for the site-specific delivery of 5-FU in colorectal cancer therapy, along with the future perspectives of these smart-delivery liposomes in colorectal cancer. In addition, this review critically highlights recent innovations in the literature on various types of stimuli-responsive liposomal formulations designed to be applied either exogenously or endogenously and that have great potential in delivering 5-FU to colorectal cancer sites.
近几十年来，5-氟尿嘧啶（5-FU）已成为应用最为广泛的抗代谢类化疗药物之一，用于治疗各类癌症。它被视为转移性结直肠癌患者的标准一线治疗药物。不幸的是，传统的5-FU化疗存在诸多局限性，比如半衰期短、生物利用度低以及细胞毒性高，会对肿瘤组织和健康组织都产生影响。为了克服5-FU的缺点并提高其对结直肠癌的治疗效果，许多研究都聚焦于设计新的给药系统，以成功将5-FU递送至肿瘤部位。脂质体作为一种被广泛认可的多种化疗药物纳米载体而受到关注。这些两亲性球形囊泡由一层或多层磷脂双层组成，除了具有生物可降解性、生物相容性、低毒性和非免疫原性等独特性质外，还显示出对疏水性和亲水性成分进行药物递送的潜力。脂质体的最新进展主要集中在化学和结构修饰方面，以在肿瘤附近特异性靶向并激活针对癌症的治疗作用。本文综述了内部刺激响应型脂质体（如由酶或pH激活的脂质体）和外部刺激响应型脂质体（如由施加磁场、光或温度变化激活的脂质体）在结直肠癌治疗中用于5-FU的位点特异性递送，以及这些智能递送脂质体在结直肠癌治疗中的未来前景。此外，本文还批判性地强调了文献中关于各种类型刺激响应型脂质体制剂的最新创新，这些制剂旨在外源性或内源性应用，并且在将5-FU递送至结直肠癌部位方面具有巨大潜力。
