Emulsion-templated synthesis and in vitro characterizations of niosomes for improved therapeutic potential of hydrophobic anti-cancer drug: tamoxifen
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Hydrophobic nature of anti-cancer drugs not only imparts different pharmacokinetic barriers in drug delivery, but also associates with off-target toxicity and low-dose exposure of drug at the tumor site which is subsequently responsible for the development of multi-drug resistance. This study describes a water-in-oil emulsion templated reverse-phase evaporation strategy, using Span 120 as non-ionic surfactant, for the synthesis of tamoxifen-loaded niosomes. The dicetyl phosphate and Span 120 were used to engineer niosomes for sustained drug release over 12 h and improved surface morphology. The spherical niosomes were 260–300 nm in size with − 34.6 mV zeta potential. The scanning electron microscopy revealed a rough texture on the surface of niosomes. Niosomes released the drug in first-order and sustained release pattern up to 12 h. Cholesterol was embedded in the outer hydrophobic surface of niosomes, via inclusion in oil phase, to enhance the interaction with lipid bilayer of the cells. Niosomes were able to improve the cellular uptake of tamoxifen and introduced apoptosis (29%) as major mechanism of cell death as compared to necrosis (17%). DSC and XRD studies revealed the crystalline nature of the drug inside niosomes while FTIR displayed chemical stability of the drug after entrapment. After encapsulation inside niosomes, the anti-cancer activity of tamoxifen was improved up to five times with IC50 reduced from 1 μM to 0.2 μM against MCF-7 cells. Cytotoxicity and sulforhodamine B assay revealed the apoptotic cell death. The unloaded niosomes alone showed no toxicity to the cells and presented a biocompatible nanoscale delivery platform for hydrophobic anti-cancer drugs.
KeywordsNiosome Tamoxifen Controlled release Breast cancer Emulsion Span 120 Cholesterol Nanomedicine
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Bakshi H et al (2010) DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from Kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev 11:675–679Google Scholar
- Baum M, Budzar A, Cuzick J, Forbes J, Houghton J, Klijn J, Sahmoud T (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet (London, England) 359:2131–2139CrossRefGoogle Scholar
- Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R, Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381:805–816CrossRefGoogle Scholar
- Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97:1652–1662CrossRefGoogle Scholar
- Javed I, Hussain SZ, Ullah I, Khan I, Ateeq M, Shahnaz G, Rehman H, Razi MT, Shah MR, Hussain I (2015) Synthesis, characterization and evaluation of lecithin-based nanocarriers for the enhanced pharmacological and oral pharmacokinetic profile of amphotericin B. J Mater Chem B 3:8359–8365CrossRefGoogle Scholar
- Mukherjee B, Patra B, Layek B, Mukherjee A (2007) Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. Int J Nanomedicine 2:213Google Scholar
- Priyadarsini RV, Murugan RS, Maitreyi S, Ramalingam K, Karunagaran D, Nagini S (2010) The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur J Pharmacol 649:84–91CrossRefGoogle Scholar
- Sun T, Zhang YS, Pang B, Hyun DC, Yang M, Xia Y (2014) Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed 53:12320–12364Google Scholar
- Wang M, Siddiqui G, Gustafsson OJR, Käkinen A, Javed I, Voelcker NH, Creek DJ, Ke PC, Davis TP (2017) Plasma proteome association and catalytic activity of stealth polymer-grafted Iron oxide nanoparticles. Small 13Google Scholar