Pedreiro Liliane Neves, Stringhetti Beatriz, Cury Ferreira, Gremião Maria Palmira Daflon
J Nanosci Nanotechnol. 2016 Feb;16(2):1248-56. doi: 10.1166/jnn.2016.11678.
Mucoadhesive drug delivery systems have been widely investigated as a strategic to allow the raising of intestinal residence time of drugs and the intimate contact with the intestinal mucosa, both factors that increase the local concentration gradient. Zidovudine (AZT) mucoadhesive nanostructured polyelectrolyte complexes were obtained by chitosan (CS)-hypromellose phthalate (HP) interactions in order to favor the permeability through biological membranes and the AZT absorption. Particle size and morphology analyses showed the obtaining of nanoparticulate delivery systems, with AZT loaded about of 65%. The characterization by DSC, X-ray diffraction and FTIR showed a new crystalline structure formed in which the drug remained molecularly dispersed, without changing this structure. The reduced release rates in the simulated gastric medium and the control of release rates in simulated intestinal medium of AZT were demonstrated by in vitro release studies. The nanoparticles liquid uptake ability associated to the mucoadhesiveness by electronic interaction between the particles and mucus revealed that the drug delivery system developed in this work is a promising approach to improve the permeation of this drug throughout the intestinal mucosa.
粘膜粘附给药系统已作为一种策略被广泛研究，该策略可延长药物在肠道的停留时间并使其与肠粘膜紧密接触，这两个因素均可增加局部浓度梯度。通过壳聚糖（CS）与邻苯二甲酸羟丙甲纤维素（HP）相互作用制备了齐多夫定（AZT）粘膜粘附纳米结构聚电解质复合物，以促进其透过生物膜的通透性及AZT的吸收。粒径和形态分析表明获得了纳米颗粒给药系统，AZT的负载量约为65%。通过差示扫描量热法（DSC）、X射线衍射和傅里叶变换红外光谱（FTIR）表征显示形成了一种新的晶体结构，药物在其中保持分子分散状态，且该结构未发生变化。体外释放研究表明，AZT在模拟胃液中的释放速率降低，在模拟肠液中的释放速率得到控制。通过颗粒与粘液之间的电子相互作用，纳米颗粒的液体摄取能力与粘膜粘附性相关，这表明本研究中开发的药物递送系统是改善该药物在整个肠粘膜中渗透的一种有前景的方法。
