Methacrylamide polymers with hydrolysis-sensitive cationic side groups as degradable gene carriers.
Water-soluble polymers with hydrolyzable cationic side groups (structure of the monomers are shown in Figure 1) were synthesized and evaluated as DNA delivery systems. The polymers, except for pHPMA-NHEM, were able to condense plasmid DNA into positively charged nanosized particles. The rate of hydrolysis at 37 degrees C and pH 7.4 of the side groups differed widely; the fastest rate of hydrolysis was observed for HPMA-DEAE (half-life of 2 h), while HPMA-DMAPr had the lowest rate of hydrolysis (half-life of 70 h). In line with this, pHPMA-DEAE-based polyplexes showed the fastest destabilization of the polyplexes at 37 degrees C and pH 7.4. Polyplexes based on pHPMA-DEAE, pHPMA-DMAE, and pHPMA-MPPM showed release of intact DNA within 24, 48, and 48 h, respectively, after incubation at 37 degrees C and pH 7.4. PHPMA-DEAE and pHPMA-MPPM based polyplexes showed the highest transfection activity (almost twice as active as pEI). Importantly, the pHPMA-DEAE, pHPMA-MPPM, and pHPMA-BDMPAP polyplexes preserved their transfection activity in the presence of serum proteins. All polymers investigated showed a substantial lower in vitro cytotoxicity than pEI. In conclusion, pHPMA-based polyplexes are an attractive class of biodegradable vectors for nonviral gene delivery.
Luten
Jordy
J
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands.
Akeroyd
Niels
N
Funhoff
Arjen
A
Lok
Martin C
MC
Talsma
Herre
H
Hennink
Wim E
WE
D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002412:Cations; D002522:Chlorocebus aethiops; D004247:DNA / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D010957:Plasmids; D011108:Polymers / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014162:Transfection
D000178:Acrylamides; D002412:Cations; D011108:Polymers; D004247:DNA; C045985:methacrylamide