Rambharose Sanjeev, Kalhapure Rahul S, Akamanchi Krishnacharya G, Govender Thirumala
Department of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, KwaZulu-Natal, South Africa.
J Mater Chem B. 2015 Aug 28;3(32):6662-6675. doi: 10.1039/c5tb00957j. Epub 2015 Jul 27.
This study was aimed at exploring the potential of unsaturated fatty acids (UFAs) [palmitoleic (PA), linoleic (LA), linolenic (LLA) and arachidonic acid (AA)], and their newly synthesized dendritic esters [PA1E, LA1E, LLA1E and AA1E] having basic tertiary nitrogen as the branching element as transdermal permeation enhancers for the delivery of tenofovir. The structures of the derivatives were confirmed by FTIR, NMR (H and C) and HRMS. The in vitro cytotoxicity study revealed their biocompatibility. Amongst the UFAs, only PA and LLA exhibited transdermal enhancer potential [enhancement ratio (ER) of 1.35 and 2.9 respectively]. All synthesized derivatives at 1% w/w were found to be more effective enhancers as compared to their parent UFAs, with LLA1E being identified as the most superior (ER = 5.31). Further, the concentration effect study revealed that at 2% w/w LLA1E had a greater ER (6.11) as compared to its parent (ER = 3.85). The permeability data correlated with the observations made in the histomorphological and transepithelial electrical resistance (TEER) evaluations. There was no significant loss in the integrity of the epidermis, transcellular and intercellular route of transport across the epidermis, with drug and enhancer treatment having no permanent damage on the epidermis. The novel dendritic ester derivatives of the UFAs therefore can be considered as effective transdermal permeation enhancers.
本研究旨在探索不饱和脂肪酸（UFA）[棕榈油酸（PA）、亚油酸（LA）、亚麻酸（LLA）和花生四烯酸（AA）]及其新合成的以碱性叔氮作为分支元素的树枝状酯[PA1E、LA1E、LLA1E和AA1E]作为替诺福韦经皮渗透促进剂的潜力。通过傅里叶变换红外光谱（FTIR）、核磁共振（H和C）以及高分辨质谱（HRMS）对衍生物的结构进行了确认。体外细胞毒性研究揭示了它们的生物相容性。在不饱和脂肪酸中，只有PA和LLA表现出经皮促进剂潜力[增强比（ER）分别为1.35和2.9]。发现所有以1%w/w浓度合成的衍生物作为经皮促进剂比其母体不饱和脂肪酸更有效，其中LLA1E被确定为最具优势的促进剂（ER = 5.31）。此外，浓度效应研究表明，与母体（ER = 3.85）相比，LLA1E在2%w/w浓度时具有更高的ER（6.11）。渗透率数据与组织形态学和跨上皮电阻（TEER）评估中的观察结果相关。表皮完整性没有显著损失，药物和促进剂处理后，药物经表皮的跨细胞和细胞间转运途径没有受到永久性损伤。因此，不饱和脂肪酸新型树枝状酯衍生物可被视为有效的经皮渗透促进剂。
