Ali Imdad, Ullah Shafi, Imran Muhammad, Saifullah Salim, Hussain Kashif, Kanwal Tasmina, Nisar Jan, Raza Shah Muhammad
H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, Karachi University, Karachi 74200, Pakistan.
National Centre of Excellence in Physical Chemistry, University of Peshawar, 25120, KpP, Pakistan.
Chem Phys Lipids. 2020 May;228:104894. doi: 10.1016/j.chemphyslip.2020.104894. Epub 2020 Feb 29.
Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 μg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B.
众多纳米技术方法已被广泛应用于提高难溶性药物的生物利用度;基于磷脂的囊泡(脂质体)是应用最广泛的药物递送系统。然而,由于稳定性问题、大规模生产限制、灭菌和长期储存问题,基于非离子表面活性剂的囊泡(非离子型脂质体)被认为是其出色的替代物。非离子型脂质体是非离子表面活性剂的囊泡,能够在其内部水相或脂质双层隔室中携带亲水性和疏水性药物。在本研究工作中,合成了基于三唑的非离子表面活性剂(TBNIS),并用不同的光谱技术对其进行了表征,然后使用NIH 3T3细胞系、血液溶血试验和小鼠急性毒性试验筛选其生物相容性。然后检查合成的表面活性剂的非离子型脂质体形成、两性霉素B负载和包封效率、药物释放,评估药物的稳定性和生物利用度,并与游离药物溶液进行比较。发现合成的表面活性剂具有生物相容性,引起的血液溶血较少,细胞活力较强,对动物的毒性可忽略不计。基于TBNIS的表面活性剂的载药非离子型脂质体囊泡大小为179.9±3.23nm,尺寸分布较小,即0.29±0.02。基于三唑的表面活性剂囊泡显示出88.76±3.45%的药物包封效率、持续的药物释放曲线和稳定性。与游离药物溶液0.012±0.023μg/mL相比,基于TBNIS的囊泡中的药物具有更高的口服生物利用度0.099±0.03。本研究结果表明,新合成的基于三唑的表面活性剂可用于药物递送,以提高两性霉素B等难溶性药物的生物利用度。