Anabousi Samah, Kleemann Elke, Bakowsky Udo, Kissel Thomas, Schmehl Thomas, Gessler Tobias, Seeger Werner, Lehr Claus-Michael, Ehrhardt Carsten
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):3010-6. doi: 10.1166/jnn.2006.461.
Oral inhalation of anticancer drugs or drug delivery system is a novel therapeutic approach in the treatment of lung cancer and requires formulations which are sufficiently stabile during nebulisation and subsequent interaction with the surfactant lining of the lungs. In this study, we assessed the stability of plain and PEGylated transferrin-conjugated liposomes after nebulisation using two different nebulisers (i.e., air-jet and ultrasonic type). Furthermore, the integrity of the liposomal membranes was assessed after incubation in commercial lung surfactant solutions (Alveofact). All liposomal formulations showed no significant changes in their size after nebulisation, independent of the type of nebuliser or the liposomal formulation, respectively. However, PEGylation was of advantage when it came to interactions between liposomes and the surfactant lining of the lungs. PEGylated liposomes were significantly more stable and retained > 80% of their drug load over 48 h, which is more than sufficient time for the drug carriers to be taken up by transferrin receptor over-expressing cancer cells in the lung. In conclusion, PEGylated and plain Tf-conjugated liposomes are stable enough to undergo nebulisation in the course of an inhalational therapy, but PEG-stabilisation results in a higher degree of membrane integrity in lung surfactant.
口服吸入抗癌药物或药物递送系统是治疗肺癌的一种新型治疗方法，需要在雾化过程中以及随后与肺表面活性剂衬里相互作用时足够稳定的制剂。在本研究中，我们使用两种不同的雾化器（即空气喷射式和超声式）评估了雾化后普通和聚乙二醇化转铁蛋白共轭脂质体的稳定性。此外，在商业肺表面活性剂溶液（Alveofact）中孵育后评估脂质体膜的完整性。所有脂质体制剂在雾化后其大小均无显著变化，分别与雾化器类型或脂质体制剂无关。然而，在脂质体与肺表面活性剂衬里的相互作用方面，聚乙二醇化具有优势。聚乙二醇化脂质体明显更稳定，在48小时内保留了超过80%的药物负载量，这对于药物载体被肺中转铁蛋白受体过表达的癌细胞摄取来说时间绰绰有余。总之，聚乙二醇化和普通转铁蛋白共轭脂质体足够稳定，可在吸入治疗过程中进行雾化，但聚乙二醇化稳定作用可使肺表面活性剂中的膜完整性更高。
