Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting

In the present study it was intended to deliver primaquine phosphate (PP), a liver schizonticide directly to liver cells using polypropyleneimine (PPI) dendrimers-coated peripherally with galactose. PPI dendrimers were synthesized by consecutive Michael double addition reaction (using ethyelenediamine as core), followed by hydrogenation reaction. Galactose conjugation was carried out by ring opening reactions, followed by Schiff's reaction and reduction to secondary amine in sodium acetate buffer (pH 4.0). IR, NMR, MASS spectroscopy were used for the confirmation of synthesis of uncoated and coated dendrimers. The formulations were made by equilibrium dialysis of dendrimers with the solution of PP. Then the formulations were characterized by TEM for size and shape. Release rate, hemolytic toxicity; bio-distribution and blood level studies were also performed on lyophilized formulations. The results obtained indicated that galactose coating of PPI systems increases the drug entrapment efficiency by 5-15 times depending upon generations. Galactose coating prolonged release up to 5-6 days as compared to 1-2 days for uncoated PPI systems. The hemolytic toxicity, blood level and hematological studies proved these systems to be safer and suitable for sustained drug delivery. Blood level studies proved the suitability of the systems for the prolonged circulations and delivery of PP to liver. The galactose coating of PPI dendrimers can therefore make the PPI systems more effective and suitable for targeted delivery of Primaquine phosphate to liver. (c) 2005 Elsevier B.V. All rights reserved.