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用疏水改性羟乙基纤维素包被的脂质体:疏水链长和改性程度的影响。

Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification.

机构信息

Department of Pharmacy, School of Pharmacy, University of Oslo, P O Box 1068, Blindern, N-0316 Oslo, Norway.

Department of Chemistry, University of Oslo, P O Box 1033, Blindern, N-0315 Oslo, Norway.

出版信息

Colloids Surf B Biointerfaces. 2017 Aug 1;156:79-86. doi: 10.1016/j.colsurfb.2017.04.061. Epub 2017 May 1.

Abstract

Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1mol% of hydrophobic groups, while 2mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4°C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4°C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4°C or in the release at 35°C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1mol% HM).

摘要

具有不带电亲水性表面的纳米颗粒系统在粘膜药物传递中可能具有很大的潜力。在本研究中,脂质体用疏水性改性羟乙基纤维素(HM-HEC)包被,以创建具有不带电表面的空间稳定的脂质体系统。目的是阐明 HEC 的疏水性修饰程度和疏水性部分的长度对系统稳定性和释放性质的影响。研究中包括具有不同疏水性修饰程度(1 和 2mol%)和不同链长的疏水性基团(C8、C12、C16)的 HM-HEC,以及流体相和凝胶相脂质体。成功地用含有 1mol%疏水性基团的 HM-HEC 包被了这两种类型的脂质体,而 2mol%的 HM-HEC 不适用于预期的药物应用。聚合物包被的凝胶相脂质体在 4°C 下稳定(大小、Zeta 电位、泄漏)24 周,C8 和 C16 HM-HEC 包被之间没有差异。对于流体相脂质体,所有制剂在 4°C 下储存 24 周后观察到粒径增大;C8 HM-HEC 包被的脂质体增加最多。在 4°C 下储存期间或在 35°C 下释放期间,在流体相制剂之间未观察到泄漏差异。总之;对于流体相脂质体,具有较短疏水性链长的 HM-HEC 导致产品稳定性降低,而对于凝胶相脂质体(1mol%HM),链长没有影响。

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