Characterization and Application of Polysaccharide-coated O/W emulsion

我们开发了一种脂质体，其用天然存在的多糖部分地被胆固醇基团取代，以使脂质体在物理化学上更稳定并且更具细胞特异性。此外，我们报道了O/W-卵磷脂乳液稳定的疏水化多糖涂层。在这项工作中，我们采用了一种新的和改进的配方，用于一种非常亲脂的液体药物，选择性细胞毒性α-亚麻酸（ALA）。本研究采用疏水化多糖CHP（cholesterol-bearing pullulan，CHP）对ALA油滴表面进行包被，并研究其体内抗肿瘤活性。加入TriC_8后，CHP/ALA乳液的胶体稳定性得到明显改善。腹腔注射CHP/ALA乳剂能有效延长MM 46乳腺癌细胞腹腔移植C3 H/He小鼠的生存期。静脉注射CHP/ALA/TriC_8乳剂后，C_3H/He小鼠皮下移植瘤的生长也受到明显抑制，而体重无明显下降。通过使用这种胶体稳定的O/W-乳剂，可以全身施用非常亲脂的液体药物。

We developed a liposome as cated with a naturally occurring polysaccharide which was partly substituted by cholesterol groups in order to make the liposome mrte physicochemically stable and more cell specific. Furthermore, we reported that O/W-lecithin emulsion is stabilized by coating with the hydrophobized polysaccharide. In this work, we employed a new and improved formulation for a very lipofilic and liquid drug, selectively cytotoxic alpha-linolenic acid (ALA). This methodology involves the colloidal stabilization of a O/W-emulsion by coating the surface of oil droplets of ALA with or without TriC_8 with a hydrophobized polysaccharide such as cholesterol-bearing pullulan, CHP and studied its in vivo antitumor activity.The O/W-emulsion was prepared by ultrasonication of a mixture of CHP and ALA in the presence or absence of trioctanoylglyceride (TriC_8). Colloidal stability of the CHP/ALA emulsion was largely improved by adding TriC_8. Intraperitoneal injection of the CHP/ALA-emulsion effectively prolonged the survial, especially, of C3H/He mice which received intraperitoneal transplantation of MM46 mammary tumore cells. The growth of the same tumor cells subcutaneously transplanted in C3H/He mice also was significantly suppressed without any loss of body weight when CHP/ALA/TriC_8-emulsion was intravenously injected. By using such the colloidally stable O/W-emulsion, a systemic administration of a very lipophilic and liquid drug became possible.