Makeiff Darren A, Smith Brad, Azyat Khalid, Xia Mike, Alam Syed Benazir
Nanotechnology Research Center, National Research Council of Canada, 11421 Saskatchewan Drive, Edmonton, Alberta T6G 2M9, Canada.
ACS Omega. 2023 Sep 6;8(37):33774-33784. doi: 10.1021/acsomega.3c04230. eCollection 2023 Sep 19.
In this study, a new drug carrier based on gelled-oil nanoparticles (GNPs) was designed and synthesized for the encapsulation and release of the model hydrophobic drug, berberine chloride (BCl). Two compositions with different oil phases were examined, sesame oil (SO) and cinnamaldehyde (Cin), which were emulsified with water, stabilized with Tween 80 (Tw80), and gelled using an N-alkylated primary oxalamide low-molecular-weight gelator (LMWG) to give stable dispersions of GNPs between 100 and 200 nm in size. The GNP formulation with Cin was significantly favored over SO due to (1) lower gel melting temperatures, (2) higher gel mechanical strength, and (3) significantly higher solubility, encapsulation efficiency, and loading of BCl. Also, the solubility and loading of BCl in Cin were significantly increased (at least 7-fold) with the addition of cinnamic acid. In vitro release studies showed that the release of BCl from the GNPs was independent of gelator concentration and lower than that for BCl solution and the corresponding nanoemulsion (no LWMG). Also, cell internalization studies suggested that the N-alkylated primary oxalamide LMWG did not interfere with the internalization efficiency of BCl into mouse mast cells. Altogether, this work demonstrates the potential use of these new GNP formulations for biomedical studies involving the encapsulation of drugs and nutraceuticals and their controlled release.
在本研究中,设计并合成了一种基于凝胶油纳米颗粒(GNP)的新型药物载体,用于包封和释放模型疏水药物氯化小檗碱(BCl)。研究了两种具有不同油相的组合物,即芝麻油(SO)和肉桂醛(Cin),它们与水乳化,用吐温80(Tw80)稳定,并使用N-烷基化伯草酰胺低分子量凝胶剂(LMWG)凝胶化,以得到尺寸在100至200nm之间的稳定GNP分散体。由于(1)较低的凝胶熔化温度,(2)较高的凝胶机械强度,以及(3)显著更高的溶解度、包封效率和BCl载量,含Cin的GNP制剂明显优于SO。此外,加入肉桂酸后,BCl在Cin中的溶解度和载量显著增加(至少7倍)。体外释放研究表明,BCl从GNP中的释放与凝胶剂浓度无关,且低于BCl溶液和相应纳米乳液(无LWMG)的释放。此外,细胞内化研究表明,N-烷基化伯草酰胺LMWG不干扰BCl进入小鼠肥大细胞的内化效率。总之,这项工作证明了这些新型GNP制剂在涉及药物和营养保健品包封及其控释的生物医学研究中的潜在用途。