The Bioscan, 4(4): 567-571, 2009
An International Quarterly Journal of Life Sciences
web site: www.thebioscan.in 
THIOLATED DENDRIMER SYSTEMS FOR THE ENHANCEMENT OF ORAL 
BIOAVAILABILITY OF AMPHOTERECIN B
SARATH K. YANDRAPU*, M LAKSHMI NARASU1 AND K.V.RAMANA MURTHY
Department of Pharmaceutical Sciences, Andhra University, Waltair - 500 003, INDIA
1Centre for Biotechnology, Institute of Science and Technology, JNTU, Hyderabad - 500 072, INDIA
E-mail: sarathky@gmail.com


KEY WORDS
Amphoterecin B Dendrimer
Bioavailability
Mucoadhesion
Oral
Drug delivery
Received on: 21.06.2009 Accepted on: 12.10.2009 *Corresponding Author

ABSTRACT

Amphotericin B (AmB), an effective antifungal and antileishmanial agent associated with low oral bioavailability and severe nephrotoxicity. The aim of the present study is to develop a new efficient formulation for enhanced oral bioavailability of AmB. The multifunctional dendrimers (Polyamidoamine, G3.5) are used in the formulation development and conjugated with cysteamine to attach thiol moiety and further chemically conjugated with AmB through EDAC mediated reaction. The synthesized conjugates are purified and duly characterized. The AmB was determined in the conjugates and found to be 8.37±1.10 (%w/w) and 19.5±2.5 (%w/w) in dendrimer-cysteamine-AmB (DCysAmB) and dendrimer-AmB (DAmB) conjugates, respectively. The free thiol content was estimated colorimetrically and found to be 42.0±1.15 (µM/mg of conjugate) in dendrimer-cysteamine conjugate (DCys). The in vitro release of AmB from DCysAmB showed an initial burst followed by controlled release behaviour in contrast to a first order faster release pattern of DAmB. In vitro rat gut loop mucoadhesion test indicated the percent mucoadhesion of DCysAmB was 3.34 and 1.17 fold higher than AmB suspension (SAmB) and DAmB respectively. The plasma drug levels found to be higher upon oral administration of DCySAmB to the rats and the Cmax was found to be 2.7 times higher to the SAmB. In view of above results it could be concluded that the thiol attached dendrimers are useful in enhancing the oral bioavailability of AmB.