To enhance the bioavailability and solubility issues of hydrophobic drugs, the development of cost-efficient nonionic surfactants has attracted scientific interest. The current study focuses on the development of phthalimide-based nonionic surfactant N, N-DPD, and its investigation as a niosomal drug delivery system for enhancing the therapeutic efficacy of curcumin (CUR). Phthalimide-based nonionic surfactant was prepared via aliphatic nucleophilic substitution reaction and characterized by diverse analytical techniques by EI-MS,1H-NMR, and 13C-NMR spectroscopy. Furthermore, the biocompatibility and non-cytotoxicity were evaluated through an MTT assay against the NIH/3T3 cell line. The outcomes showed that the average size of N, N-DPD, and CUR-N, N-DPD vesicles were (277.4 ± 6.2) and (564.7 ± 28.1) nm, and negative zeta potential values (−28.3 ± 1.28) and (−29.2 ± 1.21) mV of these niosomal vesicles were evidence their higher stability. The developed N, N-DPD, and CUR-N, N-DPD vesicles show nearly spherical morphology as elucidated by AFM and SEM images. The CUR-N, N-DPD niosomes showed high drug encapsulation efficiency of about 64.1 ± 10.6 % and higher drug release of 80 ± 2.45 % at pH 6.8. The designed CUR-N, N-DPD niosomal vesicles depicted enhanced anti-inflammatory efficacy when tested against ROS and NO generation in comparison with CUR alone. Moreover, our developed CUR-N, N-DPD vesicles show a significant apoptotic effect against the MCF-7 breast cancer cell line and compared with CUR. The outcomes of the study showed that our developed CUR-N, N-DPD vesicles are efficient in enhancing the therapeutic efficacy of CUR.
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