Faculty Collaboration Database

Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient. AAPS PharmSciTech 2005 Oct 27;6(3):E536-42

Date

12/16/2005

Pubmed ID

16354015

Pubmed Central ID

PMC2750401

DOI

10.1208/pt060367

Scopus ID

2-s2.0-27744579521 (requires institutional sign-in at Scopus site)   186 Citations

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.

Author List

Asthana A, Chauhan AS, Diwan PV, Jain NK

Author

Abhay Chauhan PhD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acids
Animals
Anti-Inflammatory Agents, Non-Steroidal
Delayed-Action Preparations
Dendrimers
Drug Delivery Systems
Male
Nanostructures
Polyamines
Rats
Rats, Sprague-Dawley