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Arginine-based cationic surfactants: Biodegradable auxiliary agents for the formation of hydrophobic ion pairs with hydrophilic macromolecular drugs.
Journal of Colloid and Interface Science ( IF 9.4 ) Pub Date : 2019-05-20 , DOI: 10.1016/j.jcis.2019.05.057 Iram Shahzadi 1 , Mulazim Hussain Asim 2 , Aida Dizdarević 1 , Julian Dominik Wolf 3 , Markus Kurpiers 3 , Barbara Matuszczak 4 , Andreas Bernkop-Schnürch 1
Journal of Colloid and Interface Science ( IF 9.4 ) Pub Date : 2019-05-20 , DOI: 10.1016/j.jcis.2019.05.057 Iram Shahzadi 1 , Mulazim Hussain Asim 2 , Aida Dizdarević 1 , Julian Dominik Wolf 3 , Markus Kurpiers 3 , Barbara Matuszczak 4 , Andreas Bernkop-Schnürch 1
Affiliation
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WORKING HYPOTHESIS
It was the hypothesis of this study that esters of arginine (Arg) with medium and long chain aliphatic alcohols are biodegradable and less cytotoxic than well-established cationic surfactants being used for hydrophobic ion pairing (HIP) with hydrophilic macromolecular drugs.
EXPERIMENTS
Arg was linked to nonan-1-ol and hexadecan-1-ol (C9 and C16) via an ester linkage. The newly formed Arg-nonyl ester (ANE) and Arg-hexadecanoyl ester (AHE) surfactants were evaluated regarding critical micelle concentration (CMC) using pyrene fluorescent method, cytotoxicity on human colorectal adenocarcinoma-derived cells (Caco-2) and biodegradability at the concentrations of 2.5 and 5 mg/mL using 2500 Nα-benzoyl-l-arginine ethyl ester hydrochloride (BAEE) units/mL of trypsin. Furthermore, in order to evaluate their potential for HIP, heparin and daptomycin were used as model polysaccharide and peptide drugs, respectively.
FINDINGS
Chemical structures of ANE and AHE surfactants were confirmed by FTIR, 1H NMR, and LC-MS. CMC of ANE was 7.5 mM and CMC of AHE was 2 mM. Arg-surfactants were not cytotoxic below their CMC. At CMC and above CMC, ANE was significantly (P < 0.05) more cytotoxic than AHE. ANE in both concentrations was degraded ˃98% within 48 h. The degradation of AHE at lower concentration was ˃97% and about 50% at higher concentration. Arg-surfactants were able to efficiently precipitate heparin and daptomycin from corresponding aqueous solutions.
CONCLUSION
Arg-surfactants being biodegradable and less toxic seems to be a promising alternative to well-established cationic surfactants for the formation of hydrophobic ion pairs (HIPs) with hydrophilic macromolecular drugs.
中文翻译：
精氨酸基阳离子表面活性剂：可生物降解的辅助剂，可与亲水性大分子药物形成疏水离子对。
假说的假设是这项研究的假设，即精氨酸（Arg）与中链和长链脂族醇形成的酯与可用于亲水性大分子药物的疏水离子配对（HIP）的阳离子表面活性剂相比，具有可生物降解性和较低的细胞毒性。实验Arg通过酯键与壬基-1-醇和十六烷-1-醇（C9和C16）相连。使用pyr荧光方法评估了新形成的Arg-壬基酯（ANE）和Arg-十六烷酸酯（AHE）表面活性剂的临界胶束浓度（CMC），对人大肠腺癌衍生细胞的细胞毒性（Caco-2）和在室温下的生物降解性浓度为2500Nα-苯甲酰基-1-精氨酸乙酯盐酸盐（BAEE）单位/ mL胰蛋白酶的浓度为2.5和5 mg / mL。此外，为了评估其在HIP中的潜力，肝素和达托霉素分别用作模型多糖和肽类药物。发现ANE和AHE表面活性剂的化学结构已通过FTIR，1H NMR和LC-MS确证。ANE的CMC为7.5 mM，AHE的CMC为2 mM。精氨酸表面活性剂在其CMC以下没有细胞毒性。在CMC和更高的CMC处，ANE的细胞毒性比AHE显着更高（P <0.05）。两种浓度的ANE在48小时内降解了约98％。在较低浓度下，AHE的降解率为˃97％，在较高浓度下，则约为50％。精氨酸表面活性剂能够从相应的水溶液中有效沉淀出肝素和达托霉素。
更新日期：2019-05-20
中文翻译：
精氨酸基阳离子表面活性剂：可生物降解的辅助剂，可与亲水性大分子药物形成疏水离子对。
假说的假设是这项研究的假设，即精氨酸（Arg）与中链和长链脂族醇形成的酯与可用于亲水性大分子药物的疏水离子配对（HIP）的阳离子表面活性剂相比，具有可生物降解性和较低的细胞毒性。实验Arg通过酯键与壬基-1-醇和十六烷-1-醇（C9和C16）相连。使用pyr荧光方法评估了新形成的Arg-壬基酯（ANE）和Arg-十六烷酸酯（AHE）表面活性剂的临界胶束浓度（CMC），对人大肠腺癌衍生细胞的细胞毒性（Caco-2）和在室温下的生物降解性浓度为2500Nα-苯甲酰基-1-精氨酸乙酯盐酸盐（BAEE）单位/ mL胰蛋白酶的浓度为2.5和5 mg / mL。此外，为了评估其在HIP中的潜力，肝素和达托霉素分别用作模型多糖和肽类药物。发现ANE和AHE表面活性剂的化学结构已通过FTIR，1H NMR和LC-MS确证。ANE的CMC为7.5 mM，AHE的CMC为2 mM。精氨酸表面活性剂在其CMC以下没有细胞毒性。在CMC和更高的CMC处，ANE的细胞毒性比AHE显着更高（P <0.05）。两种浓度的ANE在48小时内降解了约98％。在较低浓度下，AHE的降解率为˃97％，在较高浓度下，则约为50％。精氨酸表面活性剂能够从相应的水溶液中有效沉淀出肝素和达托霉素。
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