纳米载体
小泡
动态光散射
化学
肽
化学工程
纳米技术
生物物理学
药物输送
纳米颗粒
材料科学
有机化学
膜
生物化学
生物
工程类
作者
Mark Gontsarik,Amira Ben Mansour,Linda Hong,Manuel Guizar‐Sicairos,Stefan Salentinig
标识
DOI:10.1016/j.jcis.2021.06.050
摘要
pH-responsive aminolipid self-assemblies are promising platforms for the targeted delivery of antimicrobial peptides (AMPs), with the potential to improve their therapeutic efficiency and physico-chemical stability. pH-sensitive nanocarriers based on dispersed self-assemblies of 1,2-dioleoyl-3-dimethylammonium-propane (DODAP) with the human cathelicidin LL-37 in excess water were characterized at different pH values using small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. Fluorescence and electrophoretic mobility measurements were used to probe the encapsulation efficiency of LL-37 and the nanocarriers’ surface potential. Upon decreasing pH in the DODAP/water systems, normal oil-in-water emulsions at pH ≥ 5.0 transitioned to emulsions encapsulating inverse hexagonal and cubic structures at pH between 4.5 and 4.0, and mostly positively-charged vesicles at pH < 4.0. These colloidal transformations are driven by the protonation of DODAP upon pH decrease. The larger lipid-water interfacial area provided by the DODAP self-assemblies at pH ≤ 4.5 allowed for an adequate encapsulation efficiency of LL-37, favouring the formation of vesicles in a concentration-dependent manner. Contrary, LL-37 was found to dissociate from the emulsion droplets at pH 6.0. The knowledge on the pH-triggered self-assembly of LL-37 and DODAP, combined with the results on peptide release from the structures contribute to the fundamental understanding of lipid/peptide self-assembly. The results can guide the rational design of future pH-responsive AMP delivery systems.
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