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Lipomer of doxorubicin hydrochloride for enhanced oral bioavailability

1 <h5>Introduction</h5> Anthracycline antibiotic doxorubicin hydrochloride (Dox) is one of the most important cytotoxic drugs used in the treatment of a variety of hematologic malignancies and a wide range of solid tumors ( Chabner et al., 2006 ). Current chemotherapy using Dox is limited to intravenous administration of Dox as Dox solution or Dox-liposomes. Although liposomal Dox revealed significant decrease in cardio and renal toxicities ( Patil et al., 2008a,b ), administration of liposomal Dox necessitates hospitalization and is cost prohibitive.</P>Oral chemotherapy could maintain sustained therapeutic Dox concentration in the blood to improve efficacy with a possible decrease in side effects ( Bromberg, 2005 ). Oral Dox nanocarriers could provide significant improvement in patient compliance with decreased cost of therapy. Dox, a BCS class III drug and P-glycoprotein (P-gp) substrate, exhibits high first pass metabolism in liver, hence successful oral chemotherapy continues to pose serious challenges. Bromberg and Alakhov (2003) report enhanced absorption of Dox in Caco-2 cell monolayers from microgels composed of cross-linked copolymers of poly(acrylic acid) and Pluronics. Concurrent administration of Dox with myricetin enabled a 1.51–2.17 fold enhancement in oral bioavailability. This was attributed to inhibition of P-gp and reduced first-pass metabolism by inhibition of http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Pharmaceutics Elsevier
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