Department of Pharmaceutics, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt.
Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Int J Pharm. 2021 Jun 1;602:120666. doi: 10.1016/j.ijpharm.2021.120666. Epub 2021 Apr 30.
PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it's release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (-40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9%) and outstanding sustained release of only 75.4% released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.
PEGylated Liquisomes（P-Liquisomes）是一种新型药物传递系统，首次通过将磷脂复合物纳入 PEGylated 液晶纳米颗粒（P-LCNPs）中进行设计。L-肉碱（CN）是一种具有挑战性的二肽，已被证明是一种有前途的抗癌药物。然而，它具有高水溶性和广泛的体内降解，这使其无法使用。这项工作的目的是研究我们的新型系统通过延长其释放并在体内保护它来提高 CN 抗癌活性的能力。体外评估显示，包封在液晶中的球形浅色囊泡，证实了联合系统的成功形成。P-Liquisomes 为纳米尺寸（149.3 ± 1.4nm），具有高 ZP（-40.2 ± 1.5mV）、复合物效率（97.5 ± 0.9%）和出色的持续释放，仅在 24 小时后释放 75.4%，与 P-LCNPs 和 Phytosomes 相比。与 P-LCNPs 或 Phytosomes 相比，P-Liquisomes 获得的结果被认为是一个突破，特别是在处理亲水性 CN 时。体外细胞毒性评估显示，P-Liquisomes（IC = 25.9）孵育 24 小时后表现出优越的细胞毒性作用。此外，P-Liquisomes 在体内被证明是无毒的，并成功显示出优越的化学预防活性，表现为减少；肿瘤生长的百分比（7.1%）、VEGF 水平（14.3pg/g 组织）、cyclin D1 水平 15.5ng/g 组织和 caspase-3 水平升高（36.4ng/g 组织），与 Phytosomes 和 CN 溶液相比。总之，P-Liquisomes 成功地实现了 CN 的最大治疗效果，而不改变其活性，并且可以用作其他有前途的亲水性化合物的持续释放系统。
