Preparation and in vivo study of doxorubicin hcl loaded chitosan nanoparticles prepared by w/o emulsion method

The present study was carried out to determine and compare the pharmacokinetics and tissue distribution of Doxorubicin Hydrochloride (Doxorubicin) delivered as solution or through Chitosan Nanoparticles after intravenous (i.v.) injection. Doxorubicin loaded Chitosan nanoparticles were prepared by ionic gelation method (IGM). Plasma, tissue distribution profiles were quantified in an animal model of cancer and were compared to treatment with IGNP (ionic gelation method nanoparticles) to treatment with drug solution (DS). An isocratic high-pressure liquid chromatography (HPLC) method was developed to quantify Doxorubicin Hydrochloride in Rats plasma,vital organs. The Nanoparticles prepared by IGM show significantly increased the half life (T 1/2) and mean residence time (MRT) of Doxorubicin in blood. The area under curve (AUC 0-8 and AUC 0-∞) was also higher for Doxorubicin delivered through Nanoparticles prepared by both the methods, while the clearance and elimination half life (K 1/2) significantly lower. The Doxorubicin delivered through Nanoparticles experienced enhance distribution to the organs of reticuloendothelial system it lowered the distribution of Doxorubicin to heart and resulted in significantly lower concentration than Doxorubicin solution at all the time points studied. This signifies the advantage of nanoparticles in increasing the elimination half-life and reduce the Doxorubicin-associated systemic toxicity and Doxorubicin-associated cardiotoxicity.