Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Int J Pharm. 2010 May 10;390(2):234-41. doi: 10.1016/j.ijpharm.2010.02.008. Epub 2010 Feb 13.
Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The former is significantly lower than the latter (p<0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors.
转铁蛋白（Tf）-缀合脂质包被的聚（DL-丙交酯-共-乙交酯）（PLGA）纳米粒携带芳香酶抑制剂，7α-（4'-氨基）苯基硫代-1,4-雄二烯-3,17-二酮（7α-APTADD），通过溶剂注入法合成。通过优化包括 PLGA 与脂质、蛋黄卵磷脂与 TPGS、药物与 PLGA 以及合成时水相与有机相比例的制剂参数，获得了所需粒径和载药效率的纳米粒。最佳制剂的载药效率为 36.3+/-3.4%，平均粒径为 170.3+/-7.6nm，zeta 电位为-18.9+/-1.5mV。纳米粒的芳香酶抑制活性在 SKBR-3 乳腺癌细胞中进行了评价。Tf-纳米粒的 IC50 值范围为 0.77 至 1.21nM，纳米粒的 IC50 值范围为 1.90 至 3.41nM（n=3）。前者明显低于后者（p<0.05）。这些结果表明，Tf-纳米粒的芳香酶抑制活性相对于非靶向纳米粒增强，这归因于转铁蛋白受体（TfR）介导的摄取。总之，转铁蛋白缀合脂质包被的 PLGA 纳米粒是提高芳香酶抑制剂治疗递送效率和特异性的潜在载体。
