Carvalho Edison L S, Grenha Ana, Remuñán-López Carmen, Alonso Maria José, Seijo Begoña
Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Methods Enzymol. 2009;465:289-312. doi: 10.1016/S0076-6879(09)65015-1.
Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.
长期以来，设计合适的药物载体一直是药物递送领域研究人员面临的一项重大挑战。由于药物递送策略已发展为以粘膜递送作为肠胃外给药的突出替代方法，因此已开发出许多新的药物递送系统，这些系统显示出有前景的特性以解决特定问题。胶体载体，如纳米颗粒和脂质体，已被认为是最有价值的方法，但仍存在一些局限性，这些局限性可能会因给药途径的具体特性而变得更加不便。为了克服这些局限性，我们开发了一种新的药物递送系统，它是由壳聚糖纳米颗粒和脂质体结合而成，通过结合它们的优点，同时避免它们各自的局限性。因此，这些脂质/壳聚糖纳米颗粒复合物有望保护包封的药物免受恶劣环境条件的影响，同时实现其控释。为了制备这些组装体，已应用了两种不同的策略：一种是将预先形成的干燥脂质膜与壳聚糖纳米颗粒悬浮液简单水化，另一种是将两种基本结构（纳米颗粒和脂质体）冻干，随后用水化步骤。所开发的系统能够实现包封的模型肽胰岛素的控释，显示出取决于其脂质组成的释放曲线。此外，已获得令人满意的体内结果，证实了这些新开发的药物递送系统作为通过不同粘膜途径的药物载体的潜力。
