Department of Chemical & Environmental Engineering, University of Cincinnati, Cincinnati, Ohio 45221, United States.
Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221, United States.
Langmuir. 2020 Apr 7;36(13):3573-3582. doi: 10.1021/acs.langmuir.0c00215. Epub 2020 Mar 27.
Although several studies have demonstrated repetitive drug release using light-activatable liposomes, inconsistent drug release at each activation limits widespread usage. Here, we report reversible plasmonic material-coated encapsulated liposomes for proportional controlled delivery of methotrexate (MTX), which is a common drug for cancer and autoimmune diseases, using repetitive laser irradiation. Our results suggest a proportional increase in total drug release after repetitive laser irradiation. We hypothesize that the drug is released via "melted" lipid bilayers when the plasmonic materials on the liposome surface are heated by laser irradiation followed by reversible formation of the liposome. To evaluate our hypothesis, the number density of liposomes after laser irradiation was measured using single-particle (liposome) collision experiments at an ultramicroelectrode. Collisional frequency data suggest that the number density of liposomes remains unaltered even after 60 s of laser irradiation at 1.1 and 1.8 W, indicating that the liposome structure is reversible. The results were further compared with gold nanorod-coated nanodroplets where drug is released via irreversible phase transition. In contrast to what was observed with the liposome particles, the number density of the nanodroplets decreased with increasing laser irradiation duration. The structure reversibility of our liposome particles may be responsible for repetitive drug release with laser heating. We also studied the temperature rise in the lipid bilayer by incorporating polymerized 10,12-pentacosadiynoic acid (PCDA) in the lipid composition. The red shift in the UV-vis spectrum due to the structural change in PCDA lipids after laser irradiation indicates a rise in temperature above 75 °C, which is also above the chain-melting temperature of the main lipid used in the liposomes. All these results indicate that drug is released from the light-activatable liposomes due to reversible nanostructural alteration in the lipid bilayer by plasmonic resonance heating. The liposomes have potential to be a drug carrier for dose-controlled repetitive drug delivery.
尽管已有几项研究证明了可通过光活化脂质体实现药物的重复释放，但每次激活时药物释放的不一致性限制了其广泛应用。在此，我们报告了一种可逆的等离子体材料包覆的包封脂质体，用于使用重复激光照射来控制甲氨蝶呤（MTX）的比例控制释放，MTX 是癌症和自身免疫性疾病的常用药物。我们的结果表明，在重复激光照射后，总药物释放呈比例增加。我们假设，当脂质体表面的等离子体材料被激光照射加热时，药物通过“融化”的脂质双层释放，然后脂质体可逆形成。为了验证我们的假设，使用超微电极上的单颗粒（脂质体）碰撞实验测量了激光照射后脂质体的数量密度。碰撞频率数据表明，即使在 1.1 和 1.8 W 的激光照射 60 s 后，脂质体的数量密度也保持不变，表明脂质体结构是可逆的。结果与金纳米棒包覆的纳米液滴进行了比较，其中药物通过不可逆的相变释放。与观察到的脂质体颗粒相反，随着激光照射时间的增加，纳米液滴的数量密度减小。我们的脂质体颗粒的结构可逆性可能是激光加热时重复药物释放的原因。我们还通过在脂质组成中加入聚合的 10,12-二十五碳二炔酸（PCDA）来研究脂质双层中的温度升高。由于激光照射后 PCDA 脂质的结构变化，在 UV-vis 光谱中观察到红移，表明温度升高到 75°C 以上，这也高于脂质体中使用的主要脂质的链熔化温度。所有这些结果表明，由于等离子体共振加热导致脂质双层中可逆的纳米结构变化，药物从光活化脂质体中释放出来。这些脂质体有可能成为用于剂量控制的重复药物输送的药物载体。
