Tewes F, Munnier E, Antoon B, Ngaboni Okassa L, Cohen-Jonathan S, Marchais H, Douziech-Eyrolles L, Soucé M, Dubois P, Chourpa I
Université François-Rabelais, Faculté de Pharmacie Focalisation magnétique d'agents anticancéreux, IFR 135, Imagerie Fonctionnelle, Tours, France.
Eur J Pharm Biopharm. 2007 Jun;66(3):488-92. doi: 10.1016/j.ejpb.2007.02.016. Epub 2007 Feb 28.
This study describes how the control of doxorubicin (DOX) polarity allows to encapsulate it inside poly(lactide-co-glycolide) (PLGA) nanoparticles formulated either by a single oil-in-water (O/W) or a double water-in-oil-in-water (W/O/W) emulsification method (SE and DE, respectively). DOX is commercially available as a water soluble hydrochloride salt, which is useful for DE. The main difficulty related to DE approach is that the low affinity of hydrophilic drugs to the polymer limits entrapment efficiency. Compared to DE method, SE protocol is easier and should provide an additional gain in entrapment efficiency. To be encapsulated by SE technique, DOX should be used in a more lipophilic molecular form. We evaluated the lipophilicity of DOX in terms of apparent partition coefficient (P) and modulated it by adjusting the pH of the aqueous phase. The highest P values were obtained at pH ranging from 8.6 to 9, i. e. between two DOX pK(a) values (8.2 and 9.6). The conditions favorable for the drug lipophilicity were then used to formulate DOX-loaded PLGA nanoparticles by SE method. DOX encapsulation efficiency as well as release profiles were evaluated for these nanoparticles and compared to those with nanoparticles formulated by DE. Our results indicate that the encapsulation of DOX in nanoparticles formulated by SE provides an increased drug entrapment efficiency and decreases the burst effect.
本研究描述了如何通过控制阿霉素（DOX）的极性，将其封装在通过单水包油（O/W）或双水包油包水（W/O/W）乳化方法（分别为SE和DE）制备的聚（丙交酯-共-乙交酯）（PLGA）纳米颗粒中。DOX作为水溶性盐酸盐在市场上有售，这对DE方法很有用。与DE方法相关的主要困难在于亲水性药物与聚合物的低亲和力限制了包封效率。与DE方法相比，SE方案更简单，并且在包封效率方面应该会有额外的提高。要通过SE技术进行封装，DOX应以更亲脂性的分子形式使用。我们根据表观分配系数（P）评估了DOX的亲脂性，并通过调节水相的pH值对其进行了调节。在pH值为8.6至9的范围内，即两个DOX pK(a)值（8.2和9.6）之间，获得了最高的P值。然后利用有利于药物亲脂性的条件，通过SE方法制备了载DOX的PLGA纳米颗粒。对这些纳米颗粒的DOX包封效率以及释放曲线进行了评估，并与通过DE制备的纳米颗粒进行了比较。我们的结果表明，通过SE制备的纳米颗粒中DOX的封装提高了药物包封效率，并降低了突释效应。
