ABSTRACT
Controlled-release drug delivery systems are promising platforms in medicine. Among various types of material in drug delivery, hydrogels are interesting ones. They are water-soluble and tissue compatible polymers with a high capacity to carry and release drugs in a controllable manner. In this study, we introduce the synthesis, characterization, and application of an α-amylase responsive hydrogel in controlled drug delivery. The newly synthesized starch-based hydrogels structurally characterized by means of Fourier-transform infrared spectroscopy and scanning electron microscopy. A proapoptotic drug, doxorubicin, was loaded into the hydrogels and the controlled release of the drug was assessed in the presence of α-amylase and ultimately it was evaluated to controlled-drug release in vitro and subsequently in killing cancer cells. Our results highlight the effectiveness of temporal drug delivery using α-amylase responsive hydrogels in killing cancer cells.
Subject(s)
Hydrogels/chemical synthesis , Starch/analogs & derivatives , alpha-Amylases/metabolism , Cell Death , Cell Line, Tumor , Cross-Linking Reagents/chemistry , Doxorubicin/chemistry , Doxorubicin/pharmacology , Humans , Spectroscopy, Fourier Transform Infrared , Starch/metabolismABSTRACT
Cellular differentiation is one of the critical processes in the life of multicellular organisms. In this phenomenon, a non-specialized cell is converted to a specialized one with its own specific function and morphology. One of the requirements for specialization is silencing of the pathways involved in cell proliferation in parallel with turning on the molecular mechanisms involved in differentiation. Similar to other biological phenomena, the change in cellular state from the proliferative to the differentiated needs molecular switches to persuade the change in response to the internal or external inducers. The quiddity of these molecular switches has not been identified, yet. However, there exists a growing body of evidence showing that the same agents involved in apoptosis have a broad contribution to differentiation progression. To our knowledge, this evidence is still ambiguous because it has raised fundamental questions that require more proof to be answered. The most important questions are: How can two totally different cellular fates act through a similar pathway? What is the separating edge? What forces a cell to choose one of them (death or differentiation)? To address these issues, we will concentrate on three groups of molecules; caspases as the key players of apoptosis, protein kinases, and phosphatases as the major regulators of many cellular and biochemical processes. The evidence reveals a triangle of caspases, kinases, and phosphatases in which their communication leads to the fine-tuning of caspases and consequently they determine cell fate.