DODAP (1,2-Dioleoyl-3-dimethylammonium-propane) is a cationic lipid used as the lipid nanoparticle (LNP) with the pKa value of 5.59 [1]. DODAP remains largely neutral at physiological pH and becomes protonated under acidic conditions, such as those encountered during endosomal trafficking[2]. The larger lipid-water interfacial area provided by the DODAP self-assemblies at pH≤4.5 allowed for an adequate encapsulation efficiency of LL-37, favouring the formation of vesicles in a concentration-dependent manner[3]. DODAP has been widely used for efficient in vivo targeted gene delivery and possesses spleen specificity[4].
References:
[1] Carrasco M J, Alishetty S, Alameh M G, et al. Ionization and structural properties of mRNA lipid nanoparticles influence expression in intramuscular and intravascular administration[J]. Communications biology, 2021, 4(1): 956.
[2] Binici B, Rattray Z, Perrie Y. A comparative study of cationic lipid-enriched LNPs for mRNA vaccine delivery[J]. International Journal of Pharmaceutics, 2025, 682: 125941.
[3] Gontsarik M, Mansour A B, Hong L, et al. pH-responsive aminolipid nanocarriers for antimicrobial peptide delivery[J]. Journal of Colloid and Interface Science, 2021, 603: 398-407.
[4] Kimura S, Khalil I A, Elewa Y H A, et al. Novel lipid combination for delivery of plasmid DNA to immune cells in the spleen[J]. Journal of Controlled Release, 2021, 330: 753-764.
DODAP (1,2-Dioleoyl-3-dimethylammonium-propane)是一种阳离子脂质，用作脂质纳米颗粒（LNP）的组分，pKa值为5.59[1]。DODAP在生理pH值下基本保持中性，在内体运输等酸性条件下会质子化[2]。在pH≤4.5时，DODAP自组装体提供的较大脂质-水界面面积使得LL-37具有足够的包封效率，并以浓度依赖性方式促进囊泡的形成[3]。DODAP已被广泛用于高效的体内靶向基因递送，并具有脾脏特异性[4]。