Soft 3D hybrid network for delivery and controlled release of poorly soluble dihydropyrimidinone compound: An insight into the novel system for potential application in leukemia treatment.
Maja D MarkovićJulijana D TadićSanja I SavićIvana Z MatićTatjana P StanojkovićDušan Ž MijinVesna V PanićPublished in: Journal of biomedical materials research. Part A (2022)
Researchers are faced with everyday demands for safer and more efficient therapy for many diseases, especially serious one such as various types of cancer. Numerous anticancer drugs are poorly-water soluble and therefore their encapsulation and controlled release remain quite challenge. In present study, we deepened our research of hydrophilic carrier based on poly(methacrylic acid) and casein (PMAC) by investigating its potential for encapsulation and controlled release of novel poorly water-soluble dihydropyrimidion-azo-pyridon compound (DHPMP). DHPMP is a dye that has been proven to show cytotoxic activity against chronic myeloid leukemia K562 cells. By encapsulating DHPMP into the carrier and delivering it into the intestines, DHPMP absorption could be the fastest and the number of therapeutic doses and side effects can be reduced. Carriers based on PMAC and DHPMP (PMAC-DHPMP) were synthetized and characterized by FTIR, SEM and single compression tests. The swelling behavior of PMAC-DHPMP carriers and cumulative DHPMP release were investigated depending on the amount of crosslinker and encapsulated DHPMP in two media which were simulating pH environments in human stomach and intestines. The prolonged and controlled release of DHPMP was achieved. In vitro cytotoxic activity of PMAC-DHPMP carriers against K562 cells and the cell cycle analysis showed great potential of the carriers for application in leukemia treatment.
Keyphrases
- water soluble
- cell cycle
- induced apoptosis
- cell cycle arrest
- cell proliferation
- chronic myeloid leukemia
- bone marrow
- endothelial cells
- acute myeloid leukemia
- signaling pathway
- squamous cell carcinoma
- endoplasmic reticulum stress
- oxidative stress
- mass spectrometry
- combination therapy
- human health
- replacement therapy
- pi k akt
- drug induced
- smoking cessation
- highly efficient
- childhood cancer
- simultaneous determination