Synthesis of Polyamidoamine Dendrimers Having Poly(ethylene glycol) Grafts and Their Ability To Encapsulate Anticancer Drugs

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.

Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

“…Complete release of efavirenz within first 24 h from drug containing polypropylenimine (PPI) dendrimers while significantly slower release from t-Boc glycine conjugated and mannose conjugated PPI dendrimers was reported by Dutta et al (24). Drug release was also found to be controlled by molecular architecture (25) of dendrimer and introducing poly(ethylene oxide) chains on the periphery of the dendrimer (26,27). These observations suggest that further studies need to be conducted to avoid the premature release as well as control the release of SN-38 from the complexes.…”

Dendrimer-based bionanomaterials produced by surface modification, assembly and hybrid formation

“…We have shown that PEG chains can be attached to all chain ends of PAMAM G3 and G4 dendrimers by the reaction of amine-terminated dendrimers and methoxy-PEG-4-nitrophenyl carbonate (Figure 1). 11 Dendrimers of various types are shown to be capable of encapsulating small guest molecules. Indeed, PAMAM dendrimers can encapsulate various molecules.…”

“…As shown in Table 1, the dendrimers of higher generation with longer PEG chains exhibited higher encapsulation ability for both drugs, most likely because of the space created by their larger dendrimer interior and the larger hydration layers formed by PEG chains. 11 In addition, PEG-modified PAMAM dendrimers exhibited higher encapsulation ability toward methotrexate, which has two carboxyl groups in the molecule, compared with doxorubicin. Their drug-release behaviors were also examined.…”

Effect of Synthetic Polymers on tRNA Nanoparticle Formation

“…Dendrimers (Scheme 1) are also unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape with strong affinity towards DNA and RNA complexation [4][5][6][7][8][9][10]. It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

“…It has been shown that synthetic polymers induce significant changes in DNA and RNA solubility and structure under given conditions [8][9][10][11][12][13][14][15][16][17][18][19][20]. Synthetic polymers are also used to transport miRNA and siRNA in vitro [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. PEGylation of synthetic polymers such as dendrimers is shown to reduce toxicity and increase biocompatibility and DNA Transfection [6,7,9].…”