Yang Li, Yang Wenzhan, Bi Dianzhou, Zeng Qun
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Eur J Pharm Biopharm. 2006 Aug;64(1):9-15. doi: 10.1016/j.ejpb.2006.03.003. Epub 2006 Jun 22.
A novel modified film-hydration-dilution method was employed to prepare highly encapsulated interferon-alpha-2b containing liposomes for intramuscular sustained release. The liposomes produced by this technique were a mixture of mainly unilamellar vesicles and a small number of multilamellar vesicles. The trapping efficiency was above 80%. With at least 60-fold dilution, Triton X-100 at the concentration of 0.3% (w/v) in phosphate buffered saline (PBS) was able to solubilize phospholipids without denaturing the protein and/or interfering with the enzyme-linked immunoassay (ELISA). After three homogenization cycles under a pressure of 70 MPa the size of liposomes was reduced from 978 to 101 nm while the activity of interferon-alpha-2b decreased by 9.9% compared to the control. Although liposomes were physically stable for 22 months at 4 degrees C the mean size of the liposomes increased slightly from 101 to 122 nm. The levels of free interferon-alpha-2b at the site of intramuscular injection decreased rapidly with only 4.15% of initial dose retained at the injection site after 0.33 h following injection of an interferon-alpha-2b solution (nonencapsulated). In contrast, interferon-alpha-2b encapsulated in liposomes was retained at the site of intramuscular injection at higher levels than free interferon-alpha-2b (p < 0.05). Larger liposomes containing interferon-alpha-2b (978 nm) were the most effective for local retention because 27.8% of interferon-alpha-2b was retained after 24 h. These liposomes have the potential to be topically injected for treating genital herpes with prolonged interferon levels at the local injection site. Since the smaller liposomes (75.8 and 101 nm) retained interferon-alpha-2b at the injection site for shorter times while enhancing the blood circulation of the drug, they are potentially good carriers for systemic therapy with higher bioavailability and liver targeting.
采用一种新型改良的薄膜水化稀释法制备了用于肌肉内缓释的高包封率α-2b干扰素脂质体。通过该技术制备的脂质体主要是单层囊泡和少量多层囊泡的混合物。包封率高于80%。在至少60倍稀释的情况下，磷酸盐缓冲盐水（PBS）中浓度为0.3%（w/v）的Triton X-100能够溶解磷脂，而不会使蛋白质变性和/或干扰酶联免疫吸附测定（ELISA）。在70 MPa压力下经过三个均质循环后，脂质体的尺寸从978 nm减小到101 nm，而α-2b干扰素的活性与对照相比下降了9.9%。尽管脂质体在4℃下物理稳定性可达22个月，但脂质体的平均尺寸从101 nm略有增加到122 nm。肌肉注射部位游离α-2b干扰素的水平迅速下降，注射α-2b干扰素溶液（未包封）0.33小时后，仅4.15%的初始剂量保留在注射部位。相比之下，包封在脂质体中的α-2b干扰素在肌肉注射部位的保留水平高于游离α-2b干扰素（p < 0.05）。含有α-2b干扰素的较大脂质体（978 nm）对局部保留最有效，因为24小时后27.8%的α-2b干扰素被保留。这些脂质体有可能用于局部注射治疗生殖器疱疹，使局部注射部位的干扰素水平延长。由于较小的脂质体（75.8和101 nm）在注射部位保留α-2b干扰素的时间较短，同时增强了药物的血液循环，它们有可能成为具有更高生物利用度和肝脏靶向性的全身治疗的良好载体。
