Enhanced intracellular drug delivery of pH-sensitive doxorubicin/poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) nanoparticles in multi-drug resistant human epidermoid KB carcinoma cells

Biodegradable pH-sensitive amphiphilic block polymer (mPEG-Hyde-PLGA) was synthesized via ring-opening polymerization, initiated from a hydrazone-containing macro-initiator. In this way, a pH-sensitive hydrazone bond was inserted into the backbone of block copolymer, linking hydrophilic poly(ethylene glycol) segment and hydrophobic poly(lactic-co-glycolic acid) segment. The copolymer self-assembled to form stable micelles with mean diameters below 100 nm and served as a drug delivery system for doxorubicin, with drug loading content of 5.3%. pH sensitivity of the hydrazone-containing micelles was investigated by changes in diameter and size distribution observed by dynamic light scattering measurements when the micelles were encountered to acidic medium. Small pieces and larger aggregates were found by transmission electron microscopy resulting from the disassociation of the micelles in acidic conditions. It was also noted that doxorubicin release from the pH-sensitive micelles is significantly faster at pH 4.0 and pH 5.0 compared to pH 7.4, while almost no difference was detected in the case of pH non-sensitive micelles. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays on HepG-2 and MCF-7 cells revealed that doxorubicin-loaded pH-sensitive micelles had higher antitumor activity than pH-insensitive ones. This pH-sensitive drug delivery system based on hydrazone-containing block copolymer has been proved as a promising drug formulation for cancer therapy.

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Poly(ethylene glycol)-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment

Journal of Orthopaedic Translation ◽

10.1016/j.jot.2019.11.001 ◽

2020 ◽

Vol 21 ◽

pp. 57-65

Author(s):

Zhengjie Yang ◽

Qianping Guo ◽

Yan Cai ◽

Xuesong Zhu ◽

Caihong Zhu ◽

...

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Poly Ethylene Glycol ◽

Intracellular Drug Delivery ◽

Poly Ethylene

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Synthesis and characterization of pH-sensitive saccharide modified Polyurethane hydrogels: Effect of polyol, crosslinker and acid chain extender

Advanced technologies ◽

10.5937/savteh2101029k ◽

2021 ◽

Vol 10 (1) ◽

pp. 29-36

Author(s):

Marija Kostić ◽

Suzana Cakić ◽

Ivan Ristić ◽

Milena Marinović-Cincović ◽

Ljubiša Nikolić ◽

...

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Drug Delivery Systems ◽

Ph Sensitive ◽

Chain Extender ◽

Poly Ethylene Glycol ◽

Degree Of Swelling ◽

Poly Ethylene ◽

Poly Propylene

Biodegradable polyurethanes can be the basis for drug delivery systems that are sensitive to external changes. pH-sensitive polyurethanes (PUs) have been used successfully as intravaginal rings and specific drug delivery systems for the colon. In this study, a series of pH-sensitive polyurethane hydrogels with a change of the polyol component (poly(ethylene glycol) 400/poly(propylene glycol) 2000/poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) 1100), saccharides as crosslinkers (melibiose/raffinose/starch) and a-hydroxy carboxylic acids as chain extenders (dimethylol propionic acid/lactic acid) were synthesized. Structural characterization of the synthesized polyurethane hydrogels was performed using Fourier transform infrared spectroscopy (FTIR), which showed that the polyurethane synthesis reaction was achieved with successful crosslinking with saccharides and, despite the change of starting components, FTIR spectra for all investigated samples are almost identical. The degree of swelling of the hydrogels was monitored at 25 °C in solutions of pH values 4.5 and 7.4. In samples with the polyol component block1100, the degree of swelling at pH 7.4 (16.09%) was up to 9 times higher than at pH 4.5 (1.82%). The effects of variable parameters on the thermal properties and phase transitions of PUs hydrogels were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that by varying the saccharide as a crosslinker, the acid chain extender and the chain length of the polyols, the stated properties of polyurethane hydrogels as potential drug delivery carriers can be influenced.

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