Smita Pawar1, Pradeep Vavia1. 1. a Department of Pharmaceutical Sciences and Technology , Institute of Chemical Technology , Mumbai , India.
Abstract
BACKGROUND: Efficacy of an anticancer drug is challenged by severe adverse effects persuaded by the drug itself; hence designing a tumour targeted delivery system is chosen as an objective of this research work. PURPOSE: We propose, glucose transporter targeting ligand, i.e. synthesised N-lauryl glucosamine (NLG) anchored doxorubicin (DOX) in niosomal formulation. METHODS: Synthesised NLG was incorporated into niosomal formulation of DOX using Span 60 as surfactant, cholesterol as membrane stabilizer and dicetyl phosphate (DCP) as stabilizer. RESULTS: The formulation was stable with particle size of 110 ± 5 nm, zeta potential -30 ± 5 mV and entrapment efficiency approximately 95%. DSC and XRD pattern of freeze-dried formulation demonstrated encapsulation of DOX in niosomal formulation. Cytotoxicity of targeted niosomal formulation (IC50 = 0.830 ppm) was higher than non-targeted niosomal formulation (IC50 = 1.369 ppm) against B6F10 melanoma cell lines. In vitro cellular internalization revealed that targeted niosomal formulation was internalised more efficiently with higher cellular retention by cancer cells compared to the non-targeted niosomal formulation and free DOX. In vitro receptor binding and docking study of targeted niosomal formulation had shown the comparative association potential with glucose receptor. CONCLUSION: NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy.
BACKGROUND: Efficacy of an anticancer drug is challenged by severe adverse effects persuaded by the drug itself; hence designing a tumour targeted delivery system is chosen as an objective of this research work. PURPOSE: We propose, glucose transporter targeting ligand, i.e. synthesised N-lauryl glucosamine (NLG) anchored doxorubicin (DOX) in niosomal formulation. METHODS: Synthesised NLG was incorporated into niosomal formulation of DOX using Span 60 as surfactant, cholesterol as membrane stabilizer and dicetyl phosphate (DCP) as stabilizer. RESULTS: The formulation was stable with particle size of 110 ± 5 nm, zeta potential -30 ± 5 mV and entrapment efficiency approximately 95%. DSC and XRD pattern of freeze-dried formulation demonstrated encapsulation of DOX in niosomal formulation. Cytotoxicity of targeted niosomal formulation (IC50 = 0.830 ppm) was higher than non-targeted niosomal formulation (IC50 = 1.369 ppm) against B6F10 melanoma cell lines. In vitro cellular internalization revealed that targeted niosomal formulation was internalised more efficiently with higher cellular retention by cancer cells compared to the non-targeted niosomal formulation and free DOX. In vitro receptor binding and docking study of targeted niosomal formulation had shown the comparative association potential with glucose receptor. CONCLUSION: NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy.
Authors: Shuwen Liu; Huan Yue; Son Long Ho; Soyeon Kim; Ji Ae Park; Tirusew Tegafaw; Mohammad Yaseen Ahmad; Seungho Kim; Abdullah Khamis Ali Al Saidi; Dejun Zhao; Ying Liu; Sung-Wook Nam; Kwon Seok Chae; Yongmin Chang; Gang Ho Lee Journal: Int J Mol Sci Date: 2022-02-04 Impact factor: 5.923