Article

Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs.

Department of Applied Materials Science, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, Osaka 599-8531, Japan.
Bioconjugate Chemistry (impact factor: 4.93). 11(6):910-7. pp.910-7
Source: PubMed

ABSTRACT Polyamidoamine dendrimers having poly(ethylene glycol) grafts were designed as a novel drug carrier which possesses an interior for the encapsulation of drugs and a biocompatible surface. Poly(ethylene glycol) monomethyl ether with the average molecular weight of 550 or 2000 was combined to essentially every chain end of the dendrimer of the third or fourth generation via urethane bond. The poly(ethylene glycol)-attached dendrimers encapsulating anticancer drugs, adriamycin and methotrexate, were prepared by extraction with chloroform from mixtures of the poly(ethylene glycol)-attached dendrimers and varying amounts of the drugs. Their ability to encapsulate these drugs increased with increasing dendrimer generation and chain length of poly(ethylene glycol) grafts. Among the poly(ethylene glycol)-attached dendrimers prepared, the highest ability was achieved by the dendrimer of the fourth generation having the poly(ethylene glycol) grafts with the average molecular weight of 2000, which could retain 6.5 adriamycin molecules or 26 methotrexate molecules/dendrimer molecule. The methotrexate-loaded poly(ethylene glycol)-attached dendrimers released the drug slowly in an aqueous solution of low ionic strength. However, in isotonic solutions, methotrexate and adriamycin were readily released from the poly(ethylene glycol)-attached dendrimers.

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Keywords

26 methotrexate molecules/dendrimer molecule
 
6.5 adriamycin molecules
 
aqueous solution
 
average molecular weight
 
biocompatible surface
 
chain end
 
dendrimer
 
dendrimer generation
 
drugs
 
encapsulate
 
fourth generation
 
isotonic solutions
 
low ionic strength
 
methotrexate-loaded poly(ethylene glycol)-attached dendrimers
 
novel drug carrier
 
poly(ethylene glycol)
 
poly(ethylene glycol)-attached dendrimers
 
poly(ethylene glycol)-attached dendrimers encapsulating anticancer drugs
 
Polyamidoamine dendrimers
 
urethane bond
 

C. Kojima