Barbi Mariana Da Silva, Carvalho Flávia Chiva, Kiill Charlene Priscila, Barud Hernane Da Silva, Santagneli Sílvia Helena, Ribeiro Sidney José Lima, Gremião Maria Palmira Daflon
J Nanosci Nanotechnol. 2015 Jan;15(1):865-74. doi: 10.1166/jnn.2015.9180.
Zidovudine (AZT) is the antiretroviral drug most frequently used for the treatment of Acquired Immunodeficiency Syndrome. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. In this article, AZT loaded chitosan nanoparticles were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The increase proportion of CS (NP1 10:01 (w/w)) promoted the formation of smaller nanoparticles (260 nm), while raising the proportion of TPP (NP2 5:1 w/w) increased the nanoparticles size (330 nm). The incorporation of AZT increased the nanoparticles size for both AZT-loaded nanoparticles AZT-loaded NP1 (406 nm) and AZT-loaded NP2 (425 nm). The incorporation of AZT into NP1 did not change the electrophoretic mobility, however, in AZT-loaded NP2 there was a significant increase. The positive surface of the nanoparticles is very important for the mucoadhesive properties due interaction with the sialic groups of the mucin. Nuclear resonance magnetic data showed that the higher concentration of chitosan in the nanoparticles favored the interaction of few phosphate units (pyrophosphate) by ionic interaction Scanning electron microscopy, revealed that the nanoparticles are nearly spherical shape with porous surface. The entrapment efficiency of AZT, was 17.58% ± 1.48 and 11.02% ± 2.05 for NP1 and NP2, respectively. The measurement of the mucoadhesion force using mucin discs and nasal tissue obtained values of NP1 = 2.12 and NP2 = 4.62. In vitro permeation study showed that the nanoparticles promoted an increase in the flux of the drug through the nasal mucosa. In view of these results, chitosan nanoparticles were found to be a promising approach for the incorporation of hydrophilic drugs and these results suggest that the CS-containing nanoparticles have great potential for nasal AZT administration.
齐多夫定（AZT）是治疗获得性免疫缺陷综合征最常用的抗逆转录病毒药物。其口服生物利用度低，需要开发创新策略来克服首过代谢。鼻腔给药途径是提高治疗效果和降低首过效应程度的一种选择。在本文中，采用三聚磷酸钠通过改良的离子凝胶法制备了载有AZT的壳聚糖纳米粒。壳聚糖比例的增加（NP1 10:01（w/w））促进了较小纳米粒（260 nm）的形成，而提高三聚磷酸钠的比例（NP2 5:1 w/w）则增加了纳米粒的尺寸（330 nm）。AZT的掺入增加了载AZT纳米粒（载AZT的NP1（406 nm）和载AZT的NP2（425 nm））的尺寸。AZT掺入NP1中未改变电泳迁移率，然而，在载AZT的NP2中则有显著增加。纳米粒的正表面由于与粘蛋白的唾液酸基团相互作用，对粘膜粘附特性非常重要。核磁共振数据表明，纳米粒中较高浓度的壳聚糖有利于通过离子相互作用与少量磷酸单元（焦磷酸）相互作用。扫描电子显微镜显示，纳米粒接近球形，表面多孔。NP1和NP2中AZT的包封率分别为17.58%±1.48和11.02%±2.05。使用粘蛋白圆盘和鼻组织测量粘膜粘附力，NP1的值为2.12，NP2的值为4.62。体外渗透研究表明，纳米粒促进了药物通过鼻粘膜的通量增加。鉴于这些结果，发现壳聚糖纳米粒是掺入亲水性药物的一种有前途的方法，这些结果表明含CS的纳米粒在鼻腔给予AZT方面具有巨大潜力。
