Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Eur J Pharm Sci. 2014 Jul 16;58:72-82. doi: 10.1016/j.ejps.2014.04.001. Epub 2014 Apr 12.
Liquid crystalline systems (LCSs) form interesting drug delivery systems. These include in situ gelling delivery systems, which present several advantages for use as self-assembling systems for local drug delivery. The aim of this study was to develop and characterize in situ gelling delivery systems for local siRNA delivery. The influence of the components that form the systems was investigated, and the systems were characterized by polarized light microscopy, Small Angle X-ray Scattering (SAXS), swelling studies, assays of their ability to form a complex with genes and of the stability of the genes in the system, as well as assays of in situ gelling formation and local toxicity using an animal model. The system containing a mixture of monoglycerides (MO), oleylamine (OAM), propylene glycol (PG) and tris buffer (8.16:0.34:76.5:15, w/w/w/w) was considered the most appropriate for local siRNA delivery purposes. The molecular structure was characterized as hexagonal phase; the swelling studies followed a second order kinetic model and the water absorption was a fast process reaching equilibrium at 2 h. The system formed a complex with siRNA and remained in a stable form. The gel was formed in vivo after subcutaneous administration of a precursor fluid formulation in mice and was biodegradable in 30 days. The inflammatory process that took place was considered normal. Therefore, the developed liquid crystalline delivery system shows the appropriate characteristics for use as a local siRNA delivery method for gene therapy.
液晶体系（LCS）形成了有趣的药物传递系统。这些系统包括原位凝胶给药系统，其具有作为局部药物传递自组装系统的几个优点。本研究旨在开发和表征用于局部 siRNA 传递的原位凝胶给药系统。研究了形成系统的成分的影响，并通过偏光显微镜、小角 X 射线散射（SAXS）、溶胀研究、与基因形成复合物的能力、系统中基因的稳定性以及使用动物模型进行原位凝胶形成和局部毒性的测定对系统进行了表征。含有单甘油脂（MO）、油胺（OAM）、丙二醇（PG）和三羟甲基氨基甲烷缓冲液（8.16:0.34:76.5:15，w/w/w/w）混合物的系统被认为最适合用于局部 siRNA 传递目的。该分子结构被表征为六方相；溶胀研究遵循二级动力学模型，水吸收是一个快速过程，在 2 小时内达到平衡。该系统与 siRNA 形成复合物并保持稳定形式。在小鼠中给予前体液体制剂后，在体内形成凝胶，并且在 30 天内可生物降解。发生的炎症过程被认为是正常的。因此，开发的液晶给药系统显示出作为局部 siRNA 传递方法用于基因治疗的适当特性。
