Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus laboratories, 2333 CC Leiden, The Netherlands.
Leiden Institute of Chemistry, Leiden University, Gorleaus laboratories, 2333 CC Leiden, The Netherlands.
Biochim Biophys Acta Biomembr. 2018 Jun;1860(6):1272-1281. doi: 10.1016/j.bbamem.2018.02.024. Epub 2018 Feb 28.
The outermost layer of the skin, the stratum corneum (SC), acts as the natural physical barrier. The SC consists of corneocytes embedded in a crystalline lipid matrix consisting of ceramides, free fatty acids and cholesterol. Although phospholipids are frequently present in topical formulations, no detailed information is reported on the interactions between phospholipids and SC lipids. The aim of this study was to examine the interactions between a model phospholipid, dipalmitoylphosphatidylcholine (DPPC) and synthetic ceramide-based mixtures (referred to as SC lipids). (Perdeuterated) DPPC was mixed with SC lipids and the lipid organization and mixing properties were examined. The studies revealed that DPPC participates in the same lattice as SC lipids thereby enhancing a hexagonal packing. Even at a high DPPC level, no phase separated pure DPPC was observed. When a DPPC containing formulation is applied to the skin surface it must partition into the SC lipid matrix prior to any mixing with the SC lipids. To mimic this, DPPC was applied on top of a SC lipid membrane. DPPC applied in a liquid crystalline state was able to mix with the SC lipids and participated in the same lattice as the SC lipids. However, when DPPC was applied in a rippled gel-state very limited partitioning of DPPC into the SC lipid matrix occurred. Thus, when applied to the skin, liquid crystalline DPPC will have very different interactions with SC lipids than DPPC in a (rippled-)gel phase.
皮肤的最外层是角质层（SC），它起着天然物理屏障的作用。SC 由嵌入在由神经酰胺、游离脂肪酸和胆固醇组成的结晶脂质基质中的角质细胞组成。尽管磷脂经常存在于局部制剂中，但没有详细的信息报道磷脂与 SC 脂质之间的相互作用。本研究的目的是研究模型磷脂二棕榈酰磷脂酰胆碱（DPPC）与合成的基于神经酰胺的混合物（称为 SC 脂质）之间的相互作用。（氘代）DPPC 与 SC 脂质混合，研究了脂质的组织和混合特性。研究表明，DPPC 与 SC 脂质参与相同的晶格，从而增强了六方堆积。即使 DPPC 含量很高，也没有观察到相分离的纯 DPPC。当含有 DPPC 的制剂应用于皮肤表面时，它必须在与 SC 脂质混合之前分配到 SC 脂质基质中。为了模拟这种情况，将 DPPC 施加在 SC 脂质膜的顶部。以液晶状态施加的 DPPC 能够与 SC 脂质混合，并与 SC 脂质参与相同的晶格。然而，当 DPPC 以波纹凝胶状态施加时，DPPC 非常有限地分配到 SC 脂质基质中。因此，当应用于皮肤时，与 DPPC 在凝胶相（波纹凝胶相）中相比，液晶 DPPC 将与 SC 脂质有非常不同的相互作用。
