Sánchez Alejandro, Tobío María, González Libia, Fabra Angels, Alonso María J
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Eur J Pharm Sci. 2003 Mar;18(3-4):221-9. doi: 10.1016/s0928-0987(03)00019-8.
The development of new interferon-alpha (IFN-alpha) delivery strategies is a key issue in order to simplify its administration and improve its therapeutic effects, while reducing its dose-related side effects. One of the most attractive approaches towards this aim is the encapsulation of IFN-alpha into poly(lactic-glycolic acid) (PLGA) microspheres. Nevertheless, the stability of IFN-alpha released from these microspheres has been identified as one of the most important concerns in relation to the potential of this approach. Being conscious of this problem, we have used new strategies for the encapsulation of IFN-alpha into biodegradable micro- and nanoparticles. We chose poloxamer 188 as a stabilizing agent and encapsulated IFN-alpha within PLGA/poloxamer blend microspheres prepared by an oil-in-oil solvent extraction technique and also within PLGA micro- and nanospheres containing poloxamer, prepared by the water-in-oil-in-water solvent evaporation technique. The results showed that these techniques led to the efficient encapsulation of IFN-alpha and the modulation of their particle size, ranging from nanospheres (280 nm) to 40 microm-microspheres. These systems exhibit a similar pattern of release that is characterized by an initial burst (2-24% IFN-alpha released, as determined by ELISA) followed by small pulses of immunoenzymatically detected IFN-alpha for up to 1 month. The maintenance of the structural integrity and bioactivity of the protein was confirmed using a cytostasis bioassay. The results showed that the antiproliferative activity of the IFN-alpha varied depending on the formulation. More specifically, PLGA/poloxamer blend microspheres were able to provide significant amounts of active IFN-alpha for up to 96 days. This new IFN-alpha delivery system opens up possibilities to improve present IFN-alpha-based therapies.
开发新的α-干扰素（IFN-α）递送策略是一个关键问题，目的是简化其给药方式、提高治疗效果，同时减少其剂量相关的副作用。实现这一目标最具吸引力的方法之一是将IFN-α封装到聚乳酸-乙醇酸共聚物（PLGA）微球中。然而，从这些微球中释放的IFN-α的稳定性已被确定为与该方法的潜力相关的最重要问题之一。意识到这个问题后，我们采用了新的策略将IFN-α封装到可生物降解的微米和纳米颗粒中。我们选择泊洛沙姆188作为稳定剂，并将IFN-α封装在通过油包油溶剂萃取技术制备的PLGA/泊洛沙姆共混微球中，以及通过水包油包水溶剂蒸发技术制备的含有泊洛沙姆的PLGA微米和纳米球中。结果表明，这些技术能够有效地封装IFN-α并调节其粒径，范围从纳米球（280nm）到40μm的微球。这些系统呈现出相似的释放模式，其特征是初始爆发（通过ELISA测定，释放2-24%的IFN-α），随后是免疫酶法检测到的IFN-α的小脉冲释放，持续长达1个月。使用细胞生长抑制生物测定法证实了蛋白质的结构完整性和生物活性得以维持所需。结果表明，IFN-α的抗增殖活性因制剂而异。更具体地说，PLGA/泊洛沙姆共混微球能够在长达96天的时间内提供大量的活性IFN-α。这种新的IFN-α递送系统为改进目前基于IFN-α的治疗方法开辟了可能性。
