PEGylated PPI dendritic architectures for sustained delivery of H2 receptor antagonist

The present study was aimed at synthesizing and exploring the use of long circulating biocompatible PEGylated PPI 5.0G dendrimers for sustained delivery of a H-2 receptor antagonist, Famotidine. PPI 5.0G dendrimers were synthesized and PEGylated using dicarboxylic acid PEG 2000. PEGylation was confirmed by SEC, IR, NMR and MASS spectroscopies. Famotidine was loaded in PFGylated dendritic system and confirmed by IR and differential scanning calorimetry. The PEGylated dendritic system has shown an increased drug loading capacity, a reduced hemolytic toxicity and demonstrated a suitability of PEGylated PPI 5.0G dendrimer for prolonged delivery of Famotidine during in vitro release, in vivo blood level and tissue distribution studies in albino rats. The ulcer index after 5 h of treatment with different formulations was found to be 4.5 +/- 0.28 in case of plain Famotidine solution, while ulcer index was significantly reduced to 0.5 +/- 0.13 in case of Famotidine loaded PEGylated PPI 5.0G dendrimers, indicating sustained release of the drug from drug-PEGylated dendrimer complex. The results suggested that such PEGylated dendrimeric systems could serve as nanoparticulate depot for drugs in body. (C) 2008 Published by Elsevier Masson SAS.