Doxorubicin hydrochloride is extracted from a strain of Streptomyces peucetiusvarcaesius. The hydrochloride salt is a free flowing crystalline powder with a red color. The compound is soluble in methanol, acetonitrile, tetrahydrofuran, normal saline, and water; in less polar organic solvents Doxorubicin hydrochloride is only slightly soluble or insoluble. Doxorubicin hydrochloride is stable in a pH range of 3.0 to 6.5 and melts with decomposition at 205 oC.
Practical Applications of Doxorubicin Hydrochloride:
Doxorubicin is classified as an anthracycline antibiotic, used as part of a cocktail for patients 18 years and older that have metastatic breast cancer. Doxorubicin is a cytotoxic drug; it works in several ways including free radical formation, inhibition of topoisomerase II, intercalation with DNA and RNA polymerases and membrane binding. Through these mechanisms Doxorubicin is able to interact with the DNA and therefore inhibit transcription. The cancer cells can no longer divide and replicate resulting in the eventually apoptosis of the infected cell.
Unfortunately Doxorubicin is known for its many adverse side effects some of which includes myelosuppression (decreased bone marrow activity), leucopenia (low white blood cell count), neutropenia (low levels of neutrophils), neutropenic fever (a fever associated with low levels of a type of white blood cell known as neutrophils) and aleopecia (hair loss). Doxorubicin is also known to cause gastrointestinal toxicity which can present itself as nausea, vomiting and diarrhea, along with stomatitis (the inflammation of the oral cavity with or without ulceration). Doxorubicin, like all other anthracyclines, has been associated with cardiotoxicity. The induction of heart lesions or, cardiomyopathy is the leading limiting dose factor of Doxorubicin.
Due to these serious adverse side effects research is centered on finding a way to maintain the cytotoxic ability of Doxorubicin while limiting the side effects. One of these methods was to encapsulate Doxorubicin inside a liposome. Drug encapsulation inside of a liposome has some major theoretical advantages over administering free drug. One such advantage is easier intravenous administration with prolonged circulating time due to the protective effect of the liposomal membrane. However the most advantageous effect of drug encapsulation is the promotion of uptake in the appropriate organs and the lack of accumulation of liposomes in organs like the heart, kidneys, and gastrointestinal tract. This targeted delivery of Doxorubicin encapsulated liposomes is achievable due to the fact that liposomes are unable to amass in areas with tight capillary junctions; these sites include the heart muscle and the gastrointestinal tract (the leading dose limiting factors of Doxorubicin). However drug encapsulated liposomes are able to accumulate in fenestrated capillary junctions which include solid tumors and bone marrow. The drug encapsulated liposomes are also able to reach organs such as the spleen, liver and lymph nodes due to the reticuloendothelial system (RES); RES-cells all over the body uptake the liposomes and clear them from the body.
Copyright by Encapsula NanoSciences 2014
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