Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled sitespecific delivery of acidic anti-inflammatory active ingredient |
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Authors: | Abhay Asthana Abhay Singh Chauhan Prakash Vamanrao Diwan Narendra Kumar Jain |
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Institution: | (1) Department of Pharmaceutical Sciences, Dr. H. S. Gour University, 470 003 Sagar, India;(2) Pharmacology Division, Indian Institute of Chemical Technology, Habsiguda, 500 007 Tarnaka, Hyderabad, India |
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Abstract: | The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery
units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model
acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were
prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared
spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated
for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy
of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed
initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition
at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the
dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system
the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded
dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the
site of inflammation.
Published: October 27, 2005 |
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Keywords: | dendrimer flurbiprofen in vitro studies pharmacokinetics biodistribution |
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