School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Eur J Pharm Biopharm. 2022 Mar;172:101-111. doi: 10.1016/j.ejpb.2022.01.009. Epub 2022 Feb 9.
Liposome is the promising nanocarrier for pulmonary drug delivery and surface charge is its basic property. However, there is a lack of knowledge about relationship between the liposomal surface charge and its interaction with biological barriers in the lung. Therefore, the purpose of this research is to elucidate the influence of liposome surface charge on its in vivo fate. Firstly, liposomes with positive, negative and neutral surface charge were constructed and characterized, their compatibility towards pulmonary cells was studied. Then their interaction with different biological barriers in lung, including mucus, trachea, bronchoalveolar lavage fluid (BALF) and alveolar macrophage, were investigated. Their retention behavior in lung and systemic exposure were further explored. It was demonstrated that neutrally and negatively charged liposomes were safer than positively charged ones. In the conducting airway, liposome with positive surface charge could better enhance trachea distribution but only within 2 h. In the respiratory region, both neutrally and negatively charged liposomes presented improved mucus permeability, good stability in BALF containing pulmonary surfactant, decreased macrophage uptake, prolonged lung retention and decreased systemic exposure to other organs, with neutrally charged liposome showing superior performance than the negatively charged ones. While the positively charged liposome was not stable in lung microenvironment with aggregation observed, leading to increased alveolar macrophage uptake, thereby lower pulmonary retention and higher risk of systemic exposure. In conclusion, liposomal surface charge is a tunable formulation factor to modulate the interaction with biological barriers in the lung and thus in vivo fate of inhaled liposomes.
脂质体是一种很有前途的肺部药物传递的纳米载体，表面电荷是其基本性质。然而，对于脂质体表面电荷与其在肺部与生物屏障相互作用之间的关系，我们的了解还很有限。因此，本研究的目的是阐明脂质体表面电荷对其体内命运的影响。首先，构建并表征了带正、负和中性表面电荷的脂质体，研究了它们对肺细胞的相容性。然后，研究了它们与肺部的不同生物屏障（包括黏液、气管、支气管肺泡灌洗液（BALF）和肺泡巨噬细胞）的相互作用。进一步探讨了它们在肺部的保留行为和全身暴露情况。研究结果表明，中性和负电荷脂质体比正电荷脂质体更安全。在传导气道中，带正电荷的脂质体可以更好地增强气管分布，但只能在 2 小时内。在呼吸区，中性和负电荷脂质体都能提高黏液通透性，在含有肺表面活性剂的 BALF 中具有良好的稳定性，减少巨噬细胞摄取，延长肺部保留时间，减少全身向其他器官的暴露，其中中性电荷脂质体的性能优于负电荷脂质体。然而，带正电荷的脂质体在肺部微环境中不稳定，会发生聚集，导致肺泡巨噬细胞摄取增加，从而降低肺部保留率和全身暴露风险。总之，脂质体表面电荷是一个可调节的制剂因素，可以调节与肺部生物屏障的相互作用，从而影响吸入性脂质体的体内命运。
