Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles
Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles
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DOI：
10.1016/j.colsurfb.2011.02.033
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
Hadinoto, Kunn
中科院分区：
文献类型：
--
作者：
Cheow, Wean Sin;Hadinoto, Kunn
脂质-聚合物杂化纳米颗粒是由脂层包裹的聚合物纳米颗粒，它结合了脂类的高度生物相容性和聚合物纳米颗粒提供的结构完整性。认识到它们是有吸引力的药物输送载体，抗生素在本工作中被封装成用于肺部生物被膜感染治疗的杂化纳米颗粒。采用改进的乳化-溶剂-挥发法制备了杂化纳米粒子。可生物降解的聚乳酸-乙醇酸和磷脂酰胆碱分别作为聚合物和脂质模型。使用了三种氟喹诺酮类抗生素(即左氧氟沙星、环丙沙星和氧氟沙星)，它们的离子性、亲脂性和水溶解性不同。考察了杂化纳米粒的包封率、载药量、稳定性和体外释药特性。与用非脂类表面活性剂制备的聚合物纳米粒相比，除环丙沙星纳米粒外，杂化纳米粒一般较大且载药量较高。然而，杂化纳米颗粒在盐溶液中不稳定，但可以通过在配方中添加TPGS来实现稳定性。药物-脂质离子相互作用和药物亲脂性在杂化纳米粒的制备中起着重要的作用。首先，在制备过程中，相反电荷的脂质与抗生素(即环丙沙星)的相互作用导致纳米颗粒的形成失败。在药物包埋之前，必须通过添加反离子表面活性剂(如硬脂胺)使脂类的电荷反转。其次，药物的亲脂性对载药量和释药特性有很大影响，其中亲脂性较强的药物(如左氧氟沙星)具有较高的载药量和与脂膜相互作用的缓释特性。(C)2011爱思唯尔B.V.保留所有权利。
Lipid-polymer hybrid nanoparticles are polymeric nanoparticles enveloped by lipid layers that combine the highly biocompatible nature of lipids with the structural integrity afforded by polymeric nanoparticles. Recognizing them as attractive drug delivery vehicles, antibiotics are encapsulated in the present work into hybrid nanoparticles intended for lung biofilm infection therapy. Modified emulsification-solvent-evaporation methods using lipid as surfactant are employed to prepare the hybrid nanoparticles. Biodegradable poly (lactic-co-glycolic acid) and phosphatidylcholine are used as the polymer and lipid models, respectively. Three fluoroquinolone antibiotics (i.e. levofloxacin, ciprofloxacin, and ofloxacin), which vary in their ionicity, lipophilicity, and aqueous solubility, are used. The hybrid nanoparticles are examined in terms of their drug encapsulation efficiency, drug loading, stability, and in vitro drug release profile.Compared to polymeric nanoparticles prepared using non-lipid surfactants, hybrid nanoparticles in general are larger and exhibit higher drug loading, except for the ciprofloxacin-encapsulated nanoparticles. Hybrid nanoparticles, however, are unstable in salt solutions, but the stability can be conferred by adding TPGS into the formulation. Drug-lipid ionic interactions and drug lipophilicity play important roles in the hybrid nanoparticle preparation. First, interactions between oppositely charged lipid and antibiotic (i.e. ciprofloxacin) during preparation cause failed nanoparticle formation. Charge reversal of the lipid facilitated by adding counterionic surfactants (e.g. stearylamine) must be performed before drug encapsulation can take place. Second, drug loading and the release profile are strongly influenced by drug lipophilicity, where more lipophilic drug (i.e. levofloxacin) exhibit a higher drug loading and a sustained release profile attributed to the interaction with the lipid coat. (C) 2011 Elsevier B.V. All rights reserved.