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.
Similar content being viewed by others
References
Beezer AE, King ASH, Martin IK, Mitchel JC, Twyman LJ, Wain CF. Dendrimers as potential drug carriers; encapsulation of acidic hydrophobes within water soluble PAMAM derivatives.Tetrahedron. 2003;59:3873–3880.
Patri AK Jr, Majoros IJ Jr, Baker JR Jr. Dendritic polymer macromolecular carriers for drug delivery.Curr Opin Chem Biol. 2002;6:466–471.
Bosman AW, Janssen HM, Meijer EW. About dendrimers: structure, physical properties, and applications.Chem Rev. 1999;99:1665–1688.
Milhem OM, Myles C, McKeown NB, Attwood D, Emanuele AD. Polyamidoamine starburst dendrimers as solubility enhancers.Int J Pharm. 2000;197:239–241.
Kolhe P, Misra E, Kannan RM, Kannan S, Lieh-Lai M. Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers.Int J Pharm. 2003;259:143–160.
Zeng F, Zimmerman SC. Dendrimers in supramolecular chemistry: from molecular recognition to self-assembly.Chem Rev. 1997; 97:1681–1712.
Chauhan AS, Sridevi S, Chalasani KB, et al. Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin.J Control Release. 2003;90:335–343.
Khopade AJ, Caruso F, Tripathi P, Nagaich S, Jain NK. Effect of dendrimer on entrapment and release of bioactive from liposomes.Int J Pharm. 2002;232:157–162.
Khopade AJ, Shenoy DB, Khopade SA, Jain NK. Phase structures of a hydrogenated anionic phospholipid composition containing cationic dendrimers and pegylated lipids.Langmuir. 2004;20:7368–7373.
Park KM, Kim CK. Preparation and evaluation of flurbiprofenloaded microemulsion for parenteral delivery.Int J Pharm. 1999;181:173–179.
Park KM, Lee MK, Hwang KJ, Kim CK. Phospholipid-based microemulsions of flurbiprofen by the spontaneous emulsification process.Int J Pharm. 1999;183:145–154.
Government of India.Indian Pharmacopoeia. New Delhi, India: Ministry of Health and Family Welfare, Controller of Publications; 1996:328.
Singhai AK, Jain S, Jain NK. Evaluation of an aqueous injection of ketoprofen.Pharmazie. 1997;52:149–151.
Chauhan AS, Jain NK, Diwan PV, Khopade AJ. Solubility enhancement of indomethacin with poly(amidoamine) dendrimers and targeting to inflammatory regions of arthritic rats.J Drug Target. 2004;12:575–583.
Bhadra D, Bhadra S, Jain S, Jain NKA. PEGylated dendritic nanoparticulate carrier of fluorouracil.Int J Pharm. 2003;257:111–124.
Hardman JG, Limbird LE, Molinoff PB, Ruddeon RW, Gilman AG.Goodman and Gilman's the Pharmacological Basis of Therapeutics, Vol 9. New York, NY: McGraw-Hill; 1996:640–647.
Kissel M, Peschke P, Subr V, et al. Synthetic macromolecular drug carriers: biodistribution of poly[(N-2-hydroxypropyl)methacrylamide] copolymers and their accumulation in solid rat tumors.PDA J Pharm Sci Technol. 2001;55:191–201.
Crommelin DJA, Hennik WE, Strom G. Drug targeting systems: fundamentals and applications to parenteral drug delivery. In: Hillery AM, Lloyd AW, Swarbrick J, eds.Drug Delivery and Targeting. New York, NY: Taylor and Francis Inc; 2001:119–125.
Klajnert B, Stanislawska L, Bryszewska M, Palecz B. Interactions between PAMAM dendrimers and bovine serum albumin.Biochim Biophys Acta. 2003;1648:115–126.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published: October 27, 2005
Rights and permissions
About this article
Cite this article
Asthana, A., Chauhan, A.S., Diwan, P.V. et al. Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled sitespecific delivery of acidic anti-inflammatory active ingredient. AAPS PharmSciTech 6, 67 (2005). https://doi.org/10.1208/pt060367
Received:
Accepted:
DOI: https://doi.org/10.1208/pt060367