小泡
化学
动态光散射
药物输送
生物物理学
两亲性
纳米载体
查尔酮
脂质体
双层
辐照
肺表面活性物质
纳米颗粒
纳米技术
有机化学
生物化学
膜
共聚物
材料科学
生物
聚合物
物理
核物理学
作者
Dmitriy Moreira,Oren Regev,Nuno Basílio,Eduardo F. Marques
标识
DOI:10.1016/j.jcis.2023.07.129
摘要
Spatially and temporally localized delivery is a promising strategy to circumvent adverse effects of traditional drug therapy such as drug toxicity and prolonged treatments. Stimuli-responsive colloidal nanocarriers can be crucial to attain such goals. Here, we develop a delivery system based on dual light and pH responsive vesicles having a cationic bis-quat gemini surfactant, 12-2-12, and a negatively charged amphiphilic chalcone, C4SCh. The premise is to exploit the chalcone/flavylium interconversion to elicit a morphological change of the vesicles leading to the controlled release of an encapsulated drug. First, the phase behavior of the catanionic system is studied and the desirable composition yielding stable unilamellar vesicles identified and selected for further studies. The solutions containing vesicles (Dh ≈ 200 nm, ς-potential ≈ 80 mV) are in-depth characterized by light microscopy, cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and surface tension measurements. Upon subjecting the vesicles to UV irradiation (λ= 365 nm) at near neutral pH (≈ 6.0) no morphological effects are observed, yet when irradiation is coupled with pH = 3.0, the majority of the vesicles are disrupted into bilayer fragments. The anticancer drug doxorubicin (DOX) is successfully entrapped in the non-irradiated vesicles, yielding an encapsulation efficiency of ≈ 25% and a loading capacity of ≈ 3%. The release profile of the drug loaded vesicles is then studied in vitro in four conditions: i) no stimuli (pH=6.0); ii) irradiation, pH = 6.0; iii) irradiation and adjusted pH = 3.0; iv) no irradiation and pH = 3.0. Crucially irradiation at pH = 3.0 leads to a sustained release of DOX to ca. 80% (within 4 h), whereas cases i) and ii) lead to only ≈ 25 % release and case iv) to 50% release but precipitation of vesicles. Thus, our initial hypothesis is confirmed: we present a proof of concept delivery system where light and pH act as inputs of an AND logic gate mechanism for the controlled release of a relevant biomedical drug (output). This may prove useful if the irradiated nanocarriers meet acidified physiological environments such as tumors sites, endosomes or lysosomes.
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