Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 4, Issue 37, Pages 6228-6239Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6tb01841f
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Funding
- Azm & Saade Association
- Ministry of Education, Youth and Sports of CR within the National Sustainability Program I (NPU I) [POLYMAT LO1507]
- Grant Agency of the Czech Republic [15-02986S]
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The development of flexible drug delivery systems that can be tuned as a function of the drug to be delivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly( e-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design were synthesized by thiol-yne photochemistry. The grafting density and the copolymer amphiphilicity were easily controlled via the reaction parameters: concentration, reaction time, PEG length and the molar ratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behavior of the copolymers was studied and a correlation between the composition of PCL-g-PEG and the nanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L-1) was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with various drugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance in cancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug (clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7 cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratio is discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chains showed higher toxicity compared to their more hydrophilic counterparts.
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