Novel PEGylated PPI Dendritic Nanostructures for Sustained Delivery of Anti-Inflammatory Agent

Virendra      Gajbhiye; P.   Vijayraj   Kumar; Ajay      Sharma; N.   K.   Jain

doi:10.2174/157341308785161136

Abstract

The present study was aimed at developing and exploring the use of long circulating biocompatible PEGylated PPI 5.0G dendrimers for delivery of an anti-inflammatory drug, Aceclofenac. The PPI 5.0G dendrimers were synthesized and PEGylated using Nhydroxysuccinimide- activated dicarboxylic acid PEG 2000 (COOH-PEG-COOH). PEGylation was confirmed by IR, NMR and MASS spectra. The Aceclofenac was loaded in PEGylated dendritic system and various parameters like, hemolytic toxicity, drug entrapment, pH dependent in vitro drug release and in vivo blood-level were determined. The PEGylated dendritic system has shown increased drugloading capacity and reduced hemolytic toxicity as compared to non-PEGylated system. The in vitro release, in vivo blood level and tissue distribution studies in albino rats demonstrated suitability of PEGylated PPI 5.0G dendrimer for prolonged delivery of Aceclofenac. The carrageenan induced paw edema in albino rats revealed 69.41±0.7% and 77.08±0.4% inhibition of paw edema at 3rd and 7th hr, respectively that were maintained upto 52.17±0.9% until 48th hr from drug-PEGylated dendrimer complex. However, for plain drug the percentage of inhibition were found to be 66. 35±0.4% at 3rd hr, which was reduced to 28.44±0.3 % by 7th hr. PEGylation is considered to be suitable for amendment of PPI dendrimers for reducing of drug leakage and hemolytic toxicity, improving drug-loading capacity and stabilizes the system in body. The results suggested that, such PEGylated dendrimeric system is suitable for sustained delivery of Aceclofenac.

Keywords: Aceclofenac, PEGylated dendrimers, inflammation, sustained drug delivery, pharmacokinetics, pharmacodynamics

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