Novel thermosensitive small multilamellar lipid nanoparticles with promising release characteristics made by dual centrifugation

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2024-12-25 DOI:10.1016/j.ejps.2024.106999
Jonas K. Koehler , Stefanie Schmager , Johannes Schnur , Lars Gedda , Katarina Edwards , Heiko Heerklotz , Ulrich Massing
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Abstract

Thermosensitive liposomes (TSLs) have great potential for the selective delivery of cytostatic drugs to the tumor site with greatly reduced side effects. Here we report the discovery and characterization of new thermosensitive small multilamellar lipid nanoparticles (tSMLPs) with unusually high temperature selectivity. Furthermore, the temperature-dependent release of the fluorescent marker calcein from tSMLPs is enhanced by human serum albumin. tSMLPs can easily be prepared through dual centrifugation (DC) at very high lipid concentrations using dipalmitoyl and distearoyl phosphatidylcholine (DPPC, DSPC) and the phospholipid dipalmitoyl-sn-glycero-phosphatidyldiglycerol (DPPG2). The new particles have a hydrodynamic diameter of about 175 nm and a narrow size distribution (PDI 0.02). tSMLPs consist of multiple lipid membranes, which become increasingly closer packed towards the particle center, and have no visible aqueous core. The particles are highly stable due to strong hydrogen bond-based membrane interactions mediated by DPPG2. tSMLPs can be used as carriers for water-soluble drugs (EE 25 %) entrapped within the interlamellar spaces. Based on biophysical (DSC, DLS and ITC) and morphological (cryo-EM) studies, a hypothesis is presented to explain the structural basis underlying the high temperature selectivity, as well as the unusual morphology of the new thermosensitive lipid nanoparticles.

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双离心法制备具有良好释放特性的新型热敏小多层脂质纳米颗粒。
热敏脂质体(Thermosensitive liposomes, TSLs)具有将细胞抑制药物选择性递送至肿瘤部位的巨大潜力,且副作用大大降低。在这里,我们报道了具有异常高温选择性的新型热敏小多层脂质纳米颗粒(tSMLPs)的发现和表征。此外,tSMLPs中荧光标记物钙黄蛋白的温度依赖性释放被人血清白蛋白增强。利用双棕榈酰和二硬脂酰磷脂酰胆碱(DPPC, DSPC)和磷脂双棕榈酰-sn-甘油-磷脂酰二甘油酯(DPPG2),可以在非常高的脂质浓度下通过双离心(DC)制备tSMLPs。新颗粒的水动力直径约为175 nm,尺寸分布较窄(PDI为0.02)。tSMLPs由多个脂质膜组成,这些脂质膜越来越靠近颗粒中心,并且没有可见的水核。由于DPPG2介导的强氢键基膜相互作用,颗粒高度稳定。tsmlp可作为层间空间内水溶性药物(EE 25%)的载体。基于生物物理(DSC, DLS和ITC)和形态学(cro - em)研究,提出了一种假设来解释高温选择性的结构基础,以及新的热敏脂质纳米颗粒的不同寻常的形态。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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