Advances in Drug Delivery Systems for Lipophilic Drug Paclitaxel: Developments, Challenges, and Opportunities (A Review)

IF 1.1 4区 化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Russian Journal of Bioorganic Chemistry Pub Date : 2024-10-09 DOI:10.1134/S106816202405011X
Sumit Kumar, Aditi Arora, Vaishali Pant, Shramana Guchhait, Rajesh Kumar, Divya Mathur, Brajendra K. Singh
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Abstract

Paclitaxel is one of the most widely utilized anticancer drug. It displays a range of antitumor action, particularly against ovarian cancer, urologic malignancies, head tumor, and Kaposi’s sarcoma. However, due to its highly lipophilic nature, poor fluid dissolvability of less 0.01 mg/mL and lack of ionizing functionalities which may enhance its solubility, there are substantial challenges associated with Paclitaxel delivery. Paclitaxel exhibited promising effects when formulated in combination with ethanol and Cremophor EL, as Taxol®. However, it is associated with various side effects, including hypersensitivity, hypotension, and peripheral neuropathy. The albumin-based Paclitaxel, Abraxane®, is a superior alternative to Taxol® as it diminishes the side effects related to Cremophor EL. Abraxane® is regarded as the gold standard for cancer treatment, but its 21% response rate suggests that more research is needed. Furthermore, the large-scale clinical use of this drug has faced considerable delay because of the absence of suitable delivery vehicles. Therefore, necessitates is the development of an alternate form of Paclitaxel that has both superior aqueous solubility as well as fewer side-effects. During the last decade, various methodologies have been explored to improve Paclitaxel’s solubility with the help of co-solvents and inclusion complexes. Additionally, various methodologies report of passive targeting of cancer cells using nanoparticles, nanosuspensions, Rotaxane (a mechanically interlocked molecular system), liposomes, micelles, emulsions, gels, pastes, etc. Herein, we have comprised a brief report on various delivery techniques for Paclitaxel with improved therapeutic outcomes.

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亲脂性药物紫杉醇给药系统的进展:发展、挑战与机遇(综述)
紫杉醇是应用最广泛的抗癌药物之一。它具有多种抗肿瘤作用,特别是针对卵巢癌、泌尿系统恶性肿瘤、头部肿瘤和卡波西肉瘤。然而,由于紫杉醇具有高度亲脂性,在液体中的溶解度较低,仅为 0.01 毫克/毫升,而且缺乏可提高其溶解度的电离功能,因此紫杉醇的输送面临着巨大的挑战。紫杉醇与乙醇和 Cremophor EL 结合配制成 Taxol® 时,显示出良好的效果。然而,紫杉醇会产生各种副作用,包括过敏、低血压和周围神经病变。以白蛋白为基础的紫杉醇药物 Abraxane® 可减少 Cremophor EL 带来的副作用,是 Taxol® 的理想替代品。Abraxane® 被视为癌症治疗的黄金标准,但其 21% 的反应率表明还需要更多的研究。此外,由于缺乏合适的给药载体,这种药物的大规模临床应用也面临着相当大的延误。因此,有必要开发一种水溶性更好、副作用更小的紫杉醇替代品。过去十年间,人们探索了各种方法,借助助溶剂和包合物来提高紫杉醇的溶解度。此外,还有各种方法报道了利用纳米颗粒、纳米悬浮剂、Rotaxane(一种机械连锁分子系统)、脂质体、胶束、乳液、凝胶、糊剂等对癌细胞进行被动靶向治疗。在此,我们简要报告了可改善治疗效果的紫杉醇各种给药技术。
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来源期刊
Russian Journal of Bioorganic Chemistry
Russian Journal of Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
1.80
自引率
10.00%
发文量
118
审稿时长
3 months
期刊介绍: Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.
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