Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH 58 Near Baghpat Bypass, Meerut, UP, 250005, India.
Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Sector 125, Noida, Uttar Pradesh, 201301, India.
Med Oncol. 2024 Mar 25;41(5):95. doi: 10.1007/s12032-024-02319-3.
5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitro and in vivo performance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25 nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4 h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30 days. Additionally, an in vitro hemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed through in vivo pharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.
5-氟尿嘧啶（5-FU）是一种属于 BCS 分类 III 的抗癌药物，其表现出较差的释放特性和在生物系统中的低保留。本研究的主要目的是开发一种药物递送系统，即负载 5-FU 的纳米结构脂质载体（NLCs），以通过负载 5-FU 的 NLCs（5-FUNLC）延长其生物保留时间。设计 5-FUNLC 来操纵物理化学特性，并评估体外和体内性能。所开发的 NLCs 经历了全面的表征，包括粒径、zeta 电位、形态评估和傅里叶变换红外光谱（FT-IR）分析。此外，还对负载 5-FU 的 NLCs 进行了特定评估，包括药物包封效率分析、在 pH 6.8 的 PBS 中的释放特性以及稳定性研究。通过测定分配系数（log P）来确认 5-FUNLC 的亲脂性。负载 5-FU 的 NLCs 观察为平均粒径为 300±25nm 的球形颗粒。包封效率被确定为 89%，表明药物在 NLCs 内得到有效负载。此外，这些 NLCs表现出持续释放特性，持续时间长达 3-4 小时，表明它们具有随时间控制药物释放的潜力。脂质成分与 5-FU 具有生物相容性，以确定热转变温度，并在 30 天内表现出良好的稳定性。此外，通过静脉内给药，进行了体外溶血研究，以确认该系统不会对 RBC 造成任何破坏。通过优化的负载 5-FU 的 NLC（F2）与通过肠或肠囊模型（从顶侧向基底外侧，A→B）的 5-FU 相比，评估了药物的肠道通透性。测量渗透率系数为 4.91×10cm/h，具有显著差异。此外，通过 DPPH 法证明了 NLCs 的抗氧化潜力。通过在 Wistar 大鼠上进行体内药代动力学研究进一步评估了 NLCs 的性能，与游离 5-FU 相比，其活性提高了 1.5 倍。这些 NLCs 提高了药物的溶解度和持续释放，共同提高了治疗效果并调节了生物利用度。研究得出结论，负载 5-FU 的 NLC 具有作为创新和有效的药物递送系统的潜力。研究结果表明，有必要进行进一步的临床前研究，为开发更有效和耐受良好的癌症治疗方法开辟了有前景的途径。
