Polyamidoamine dendrimers as a novel oral drug delivery system :
Synthesis and characterisation of dendrimer-ibuprofen conjugates
Ruedeekorn Wiwattanapatapee, Asst. Prof., D. of Pharmaceutical Tech., F. of Pharmaceutical Sci., PSU.
Ruth Duncan, Centre for Polymer Therapeutics, The School of Pharmacy, U. of London, UK.
Corresponding e-mail : wruedeek@ratree.psu.ac.th
Published : Thai J Pharm Sci 2000, 24(Suppl.) : 67
Key words : PAMAM dendrimers, oral delivery
Dendrimers are monodisperse, spherical hyperbranched synthetic macromolecules with a large
number of surface groups that have the potential as oral drug delivery systems. These nanoparticulate carriers can theoretically carry drugs by covalent binding or complexation to the dendrimer surface, or by entrapment within the dendrimer core. Previously, we have described the biocompatibility of polyamidoamine (PAMAM) dendrimers and also other families of dendrimers. In the context of oral delivery, dendrimers could theoretically control the release of bound or complexed drug site-specifically during transit in the GI tract, and indeed the in vitro studies have shown that anionic PAMAM dendrimers rapidly transfer across the everted rat intestinal sac model.
In this study ibuprofen and PAMAM dendrimer generation 3 were used as a preliminary model drug-dendrimer conjugates. The carboxylic groups of the drug were attached to the amine surface
via amide bond using carbodiimide linker. The conjugates were purified and characterised by se-phadex G-25 column chromatography. The structure of dendrimer-drug conjugate was confirmed by HPLC. A maximal loading of 13.4% wt% and a molar ratio of 1 dendrimer to 4 ibuprofen molecules was obtained (30.2% efficiency) and the amount of free ibuprofen in the conjugate was 0.08% of
the total ibuprofen bound. The synthetic approach in this study has shown the possibility to prepare
well characterised conjugates and in future the pharmacokinetics in vivo after oral administration of the conjugates will be investigated.
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