TPP /壳聚糖纳米粒子的合成和表征：反应的胶体机理和对白色念珠菌生物膜形成的抗真菌作用。,Biomaterials Advances

在本研究中，使用三聚磷酸盐（TPP）作为交联剂，通过离子凝胶化工艺合成了壳聚糖（Chit）纳米粒子。通过滴定评估TPP / Chit纳米颗粒的形成，通过等温量热法（ITC）测量电导率（k），ζ电位（ZP），流体动力学直径（D h），粘度（η）和热量。通过与白色抑菌素和壳聚糖相比，通过白色念珠菌时间杀灭试验，白色念珠菌初始粘附抑制和生物膜形成的抑制作用评估抗真菌作用。电导滴定法显示出典型的沉淀曲线，在[TPP] / [Chit mon ]  ≈0.3的摩尔比处出现拐点，表明化学计量比为1：3.3。最高Dh，ZP和η值在滴定开始时显示，因为Chit-Chit之间存在分子内排斥。添加TPP后，该值逐渐降低，在[TPP] / [Chit mon ]  ≈0.16时发生中间过渡，这归因于链间交联的部分分解和离散带电聚集体的形成。此后，应通过中和这些装配体来发生反应，从而使D h，ZP和η的值再次降低，直到[TPP] / [Chit mon ]  ≈0.3，直到它们达到最低值。ITC实验还表明发生了两种结合（K 1  = 3.6×10 3和K 2  = 7.7×10 4），这是由熵驱动的。生物学结果显示，与壳聚糖和制霉菌素相比，MIC和2 MIC在24 h内TPP / Chit的白色念珠菌活力较低。此外，TPP / Chit对白色念珠菌粘附和生物膜形成的抑制作用为25–50％。结果表明，TPP / Chit纳米颗粒降低了白色念珠菌的初始粘附力和生物膜形成，并显示了用于治疗口腔念珠菌病的制剂的潜力。

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In the present study chitosan (Chit) nanoparticles were synthetized by the ionic gelation process, using tripolyphosphate (TPP) as crosslinking agent. The TPP/Chit nanoparticle formation was evaluated by titrations, measuring electrical conductivity (k), zeta potential (ZP), hydrodynamic diameter (Dh), viscosity (η) and heat by isothermal calorimetry (ITC). The antifungal effects were evaluated by C. albicans time-kill assays, inhibition of C. albicans initial adhesion and biofilm formation in comparison with nystatin and chitosan. Conductometric titration exhibited a typical precipitation profile, with an inflection at molar ratio of [TPP]/[Chitmon] ≈ 0.3, suggesting a 1:3.3 stoichiometry. The highest Dh, ZP and η values were shown at the beginning of titrations, due to the intramolecular repulsion between Chit-Chit. With addition of TPP, the values showed gradual reduction, with an intermediary transition at [TPP]/[Chitmon] ≈ 0.16, which was attributed to the partial breakdown of interchain crosslinking and formation of discrete charged aggregates. After this point, reaction should occur by neutralization of these assemblies, causing new reduction in values of Dh, ZP and η until [TPP]/[Chitmon] ≈ 0.3, when they reached their lowest values. ITC experiment also showed the occurrence of two bindings (K1 = 3.6 × 103 and K2 = 7.7 × 104), which were entropy driven. Biological results showed lower C. albicans viability for TPP/Chit over 24 h compared with chitosan and nystatin at MIC and 2 MIC. Moreover, TPP/Chit showed 25–50% inhibition of C. albicans adhesion and biofilm formation. The results showed that TPP/Chit nanoparticles reduced the initial adhesion and biofilm formation of C. albicans and demonstrated potential for use in a formulation for the treatment of oral candidiasis.