Doroshenko Kateryna Mykhailivna, Shefchenko Oleksander Ivanovich
Department of Chemistry, Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine.
Department of Chemistry, Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine.
Bioorg Med Chem Lett. 2025 Dec 15;129:130396. doi: 10.1016/j.bmcl.2025.130396. Epub 2025 Sep 4.
Phospholipid-derived nanocarriers represent a versatile and chemically customizable class of drug delivery systems that self-assemble into bilayered vesicles due to their intrinsic amphiphilicity. These systems can encapsulate both hydrophilic and hydrophobic drugs through non-covalent interactions and manipulation of lipid phase behavior. This review examines the molecular and supramolecular principles underlying the formation, stability, and functional performance of key phospholipid-based nanocarriers-including liposomes, transferosomes, ethosomes, invasomes, phytosomes, pharmacosomes, and virosomes. We analyze critical structural parameters such as bilayer packing, surface charge, curvature elasticity, and membrane permeability, emphasizing their impact on drug loading efficiency, controlled release, and bioavailability. Advanced multilamellar systems such as vesosomes and spongosomes are also highlighted for their promise in achieving site-specific, sustained drug delivery. Key fabrication methods-including thin-film hydration, ethanol injection, freeze-thaw cycles, and microfluidics-are discussed alongside analytical techniques such as dynamic light scattering (DLS), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and cryo-transmission electron microscopy (cryo-TEM). The review further explores the translational landscape, with a focus on clinically approved liposomal formulations, patent developments, and emerging clinical trials involving stimuli-responsive systems. Persistent challenges such as colloidal stability, tumor penetration, immune system interactions, and scalable manufacturing are critically assessed. Altogether, this review offers a chemistry-focused framework for the rational design and clinical translation of phospholipid nanocarriers in cancer drug delivery.
磷脂衍生的纳米载体是一类多功能且可化学定制的药物递送系统，由于其固有的两亲性可自组装成双层囊泡。这些系统可通过非共价相互作用以及对脂质相行为的调控来包封亲水性和疏水性药物。本综述研究了关键的基于磷脂的纳米载体（包括脂质体、传递体、醇质体、侵入体、植物脂质体、药物体和病毒体）形成、稳定性和功能性能背后的分子和超分子原理。我们分析了诸如双层堆积、表面电荷、曲率弹性和膜通透性等关键结构参数，强调了它们对药物负载效率、控释和生物利用度的影响。还突出了先进的多层系统，如泡囊和海绵体在实现位点特异性、持续药物递送方面的前景。讨论了关键的制备方法，包括薄膜水化法、乙醇注入法、冻融循环法和微流控法，以及诸如动态光散射（DLS）、差示扫描量热法（DSC）、傅里叶变换红外光谱法（FTIR）和冷冻透射电子显微镜法（cryo-TEM）等分析技术。该综述进一步探讨了转化前景，重点关注临床批准的脂质体制剂、专利进展以及涉及刺激响应系统的新兴临床试验。对诸如胶体稳定性、肿瘤渗透、免疫系统相互作用和可扩展制造等持续存在的挑战进行了严格评估。总之，本综述为癌症药物递送中磷脂纳米载体的合理设计和临床转化提供了一个以化学为重点的框架。
