الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Alkylphosphocholines (APCs) are a group of drugs originally discovered for their anticancer effects. Later, they were found to be of a broad spectrum of activity which is mostly due to their unique action on the cell membrane. Beside their anticancer effects, APCs were effective against fungal, bacterial and protozoal infections. Miltefosine, the prototype of APCs is the most widely investigated of the class. It is currently used for the topical treatment of cutaneous metastasis of breast cancer and was recently approved by the FDA as the first and the only oral drug for the treatment of leishmaniasis, a neglected tropical disease (NTD).
Neglected tropical diseases (NTDs) are a group of 18 diseases afflicting more than one billion of the lowest income people in tropical and subtropical regions and presenting an enormous global health and economic burden. Among these, human schistosomiasis is one of the most prevalent parasitic disease affecting the poor mostly in tropical and subtropical underdeveloped countries. The disease burden for schistosomiasis, from 2000-2012 was estimated to be between 4.02 and 3.14 million DALYs. These values may be considered as underestimated due to the secondary morbidities caused by the disease.
Effective control of schistosomiasis is challenged by continuous spread of the disease to new geographic areas, lack of a licensed vaccine and the dependence of chemotherapy solely on praziquantel (PZQ) as the standard treatment. Reliance on a single drug makes the prospect of emerging drug resistance particularly worrisome. Another challenge to PZQ monotherapy is poor susceptibility of immature worms to the chemotherapeutic action of PZQ. Thus, alternative inexpensive antischistosomal chemotherapies are acutely needed. Major hurdles in this respect include high cost and failure rates of the lengthy procedure of drug discovery and development. These are augmented by reluctance of drug companies to invest in drug products for impoverished countries.
Repurposing of existing drug molecules and the use of drug delivery technologies to improve the efficacy and safety of current and repurposed drugs provide attractive less time consuming and lower cost approaches. Interesting promising results were obtained when visiting the anticancer drugs, since parasites have several of the common characteristics of malignant tumors.
Miltefosine (MFS) was recently shown to be highly effective against schistosomiasis with a broad spectrum of activity. In vivo testing against S. mansoni in the mouse model revealed significant antischistosomal activity using five successive 20 mg/kg/day oral doses of MFS solution and effectiveness against different developmental stages of the parasite, pointing out rediscovery of MFS as a potential antischistosomal agent. However, the five-dose regimen for MFS therapy would not allow mass chemotherapy. Thus, research efforts are needed to enhance the antischistosomal activity of MFS to allow for a single oral dose treatment. The pharmaceutical nanotechnological literature provided evidence for enhancement of anti-parasitic activity of diverse drugs when administered as drug delivery systems.