Abstract
The synthesis and characterisation of novel polyphosphazene nanocarriers, based on hydrophilic polyalkylene oxide Jeffamine M1000 and hydrophobic steroids with a glycinate linker for pH-controlled release of diosgenin and two brassinosteroids (DI31 and S7) with agrochemical and potential anticancer activity, is hereby described. Polyphosphazenes carrying approximately 17 wt% of DI31 or S7 self-assembled in water to form 120-150 nm nanoaggregates, which showed an excellent plant growth effect on radish cotyledons due to sustained delivery of approximately 30% of the agrochemicals after 4 days. Cytotoxic evaluation showed that all polymers carrying steroids and Jeffamine M1000 resulted in strong to moderate toxicity to MCF-7 cancer cells and were non-toxic to primary human lung fibroblast cells at 0.1 to 0.025 mg mL-1. Thus, DI31 and S7 bearing polymers applied at 10-4 to 10-6 mg mL-1 for delivery of recommended DI31 or S7 quantities to crops should be harmless to humans. Particularly, DI31 and S7 bearing polymers with strong cytotoxicity on MCF-7 and non-toxicity on primary human lung fibroblasts, good cell uptake after 6 hours, proper hydrodynamic sizes between 100 and 200 nm, and slow sustained release of cytotoxic drugs (DI31, S7) in acidic conditions might potentiate their accumulation in cancer tissues with good antitumour effects and minor side effects. These results demonstrated that preparation of brassinosteroid bearing polymers is a promising strategy for the preparation of better agrochemicals with reduced pollutant impact on sustainable agriculture and potential anticancer formulations based on analogues of brassinosteroids.
Highlights
PaperJournal of Materials Chemistry B than pharmaceuticals.[16]
Cytotoxic evaluation showed that all polymers carrying steroids and Jeffamine M1000 resulted in strong to moderate toxicity to MCF-7 cancer cells and were non-toxic to primary human lung fibroblast cells at 0.1 to 0.025 mg mLÀ1
Synthesis and characterisation of polymers P1–P6 Polyphosphazenes with diosgenin as a model-drug and Jeffamine M1000 were first synthesised with a ratio of initiator to monomer of 1 : 25 and 1 : 50, and a ratio of substituents diosgenin to Jeffamine M1000 of 1 : 1 and 1 : 2 (Table 1)
Summary
Journal of Materials Chemistry B than pharmaceuticals.[16] In this sense, an ideal drug delivery system for application in agriculture should provide sustained release of the agrochemical, achieving a high drug loading with retained activity, good solubility and stability in water under normal usage conditions (pH 7.0, 25 1C), together with proper degradation and no toxicity of the polymer matrix and its metabolites in plants and animals.[17,18] polyphosphazenes, a group of degradable synthetic polymers with highly tuneable composition and properties, appear to be promising candidates to this end. Diosgenin itself has shown good antidiabetic, hypocholesterolemic, antithrombotic and anticancer activity, but very low aqueous solubility and reduced oral bioavailability limit its medical applications.[19,21] some brassinosteroids and synthetic analogues of brassinosteroids have displayed potent antiproliferative effects on different cancer cells with reduced haemolysis and negative effects on non-cancer cells.[22,23] This is the reasoning behind designing an efficient polyphosphazene-based drug delivery system for diosgenin and brassinosteroids
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
