Funakoshi Yuka, Iwao Yasunori, Noguchi Shuji, Itai Shigeru
Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka.
Chem Pharm Bull (Tokyo). 2015;63(9):731-6. doi: 10.1248/cpb.c15-00077.
Previously, we developed lipid nanoparticles (LNs) containing poorly water-soluble drugs using two types of phospholipids, a neutral phospholipid (hydrogenated soybean phosphatidylcholine) and a negatively-charged phospholipid (dipalmitoylphosphatidylglycerol), with mean particle sizes of less than 100 nm. Here, we studied the effects of alkyl chain length and unsaturation of neutral and negatively-charged phospholipids on the physicochemical properties of LNs. Three neutral phospholipids, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine, having different alkyl chain lengths, were compared. The mean particle size of the LNs increased with the alkyl chain length, while the concentration of the drug entrapped in the LNs decreased. The particle size of all of the LNs could be maintained at less than 100 nm for 1 month in cool and dark conditions, with the LNs with longer alkyl chain lipids showing greater stability. In the unsaturated phospholipids, the double bond in the alkyl chain of dioleoylphosphatidylcholine and dierucoylphosphatidylcholine did not affect the physicochemical properties of the LNs. The negatively-charged phospholipids dipalmitoylphosphatidylglycerol and distearoylphosphatidylglycerol were also compared; LNs with longer alkyl chain lipids had larger particle sizes and lower drug concentrations, similar to the results for neutral phospholipids. We concluded that although some changes in physicochemical properties were observed among LNs with different phospholipid alkyl chain lengths, this methodology was general. LNs with suitable physicochemical properties could be prepared irrespective of the type of phospholipids used.
此前，我们使用两种磷脂（一种中性磷脂（氢化大豆磷脂酰胆碱）和一种带负电荷的磷脂（二棕榈酰磷脂酰甘油））开发了含有难溶性药物的脂质纳米粒（LNs），其平均粒径小于100 nm。在此，我们研究了中性和带负电荷的磷脂的烷基链长度和不饱和度对LNs理化性质的影响。比较了三种具有不同烷基链长度的中性磷脂，即二肉豆蔻酰磷脂酰胆碱、二棕榈酰磷脂酰胆碱和二硬脂酰磷脂酰胆碱。LNs的平均粒径随烷基链长度增加而增大，而包裹在LNs中的药物浓度降低。在阴凉黑暗条件下，所有LNs的粒径在1个月内均可维持在小于100 nm，烷基链脂质较长的LNs表现出更高的稳定性。在不饱和磷脂中，二油酰磷脂酰胆碱和二芥酰磷脂酰胆碱烷基链中的双键不影响LNs的理化性质。还比较了带负电荷的磷脂二棕榈酰磷脂酰甘油和二硬脂酰磷脂酰甘油；与中性磷脂的结果相似，烷基链脂质较长的LNs粒径较大且药物浓度较低。我们得出结论，尽管在具有不同磷脂烷基链长度的LNs之间观察到了一些理化性质的变化，但该方法具有通用性。无论使用何种类型的磷脂，都可以制备出具有合适理化性质的LNs。
