Jores Katja, Haberland Annekathrin, Wartewig Siegfried, Mäder Karsten, Mehnert Wolfgang
Department of Pharmaceutical Technology, Institute of Pharmacy, Free University of Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
Pharm Res. 2005 Nov;22(11):1887-97. doi: 10.1007/s11095-005-7148-5.
PURPOSE: Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to overcome the poor drug loading capacity of solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets, which are embedded in a solid lipid matrix. High loading capacities and controlled release characteristics have been claimed. It is the objective of the present paper to investigate these new NLC particles in more detail to obtain insights into their structure. METHODS: Colloidal lipid dispersions were produced by high-pressure homogenization. Particle sizes were estimated by laser diffraction and photon correlation spectroscopy. The hydrophobic fluorescent marker nile red (NR) was used as model drug, and by fluorometric spectroscopy, the molecular environment (polarity) was elucidated because of solvatochromism of NR. The packaging of the lipid nanoparticles was investigated by Raman spectroscopy and by densimetry. The light propagation in lipid nanodispersions was examined by refractometry to obtain further insights into the nanostructural compositions of the carriers. RESULTS: Fluorometric spectroscopy clearly demonstrates that NLC nanoparticles offer two nanocompartments of different polarity to accommodate NR. Nevertheless, in both compartments, NR experiences less protection from the outer water phase than in a nanoemulsion. In conventional SLN, lipid crystallization leads to the expulsion of the lipophilic NR from the solid lipid. Measurements performed by densimetry and Raman spectroscopy confirm the idea of intact glyceryl behenate lattices in spite of oil loading. The lipid crystals are not disturbed in their structure as it could be suggested in case of oil incorporation. Refractometric data reveal the idea of light protection because of incorporation of sensitive drug molecules in NLC. CONCLUSION: Neither SLN nor NLC lipid nanoparticles did show any advantage with respect to incorporation rate compared to conventional nanoemulsions. The experimental data let us conclude that NLC lipid nanoparticles are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.
目的:最近,有人描述了由固体和液体脂质混合物制成的胶体分散体,以克服固体脂质纳米粒(SLN)药物负载能力差的问题。有人提出,这些纳米结构脂质载体(NLC)由嵌入固体脂质基质中的油滴组成。据称其具有高负载能力和控释特性。本文的目的是更详细地研究这些新型NLC颗粒,以深入了解其结构。 方法:通过高压均质法制备胶体脂质分散体。通过激光衍射和光子相关光谱法估计粒径。疏水性荧光标记尼罗红(NR)用作模型药物,由于NR的溶剂化显色作用,通过荧光光谱法阐明分子环境(极性)。通过拉曼光谱法和密度测定法研究脂质纳米粒的包封情况。通过折射测定法检查脂质纳米分散体中的光传播,以进一步深入了解载体的纳米结构组成。 结果:荧光光谱法清楚地表明,NLC纳米粒提供了两个不同极性的纳米隔室来容纳NR。然而,在这两个隔室中,与纳米乳液相比,NR受到的来自外部水相的保护更少。在传统的SLN中,脂质结晶导致亲脂性NR从固体脂质中排出。密度测定法和拉曼光谱法进行的测量证实了尽管有油负载,但山嵛酸甘油酯晶格仍保持完整的观点。脂质晶体的结构没有像在掺入油的情况下可能暗示的那样受到干扰。折射测定数据揭示了由于在NLC中掺入敏感药物分子而产生光保护的观点。 结论:与传统纳米乳液相比,SLN和NLC脂质纳米粒在掺入率方面均未显示出任何优势。实验数据使我们得出结论,NLC脂质纳米粒不是带有嵌入液滴的球形固体脂质颗粒,而是固体薄片,在固体薄片和表面活性剂层之间存在油。
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