PMID- 22145672 OWN - NLM STAT- MEDLINE DCOM- 20120424 LR - 20220414 IS - 1526-4602 (Electronic) IS - 1525-7797 (Linking) VI - 13 IP - 1 DP - 2012 Jan 9 TI - Biodegradable poly(vinyl alcohol)-polyethylenimine nanocomposites for enhanced gene expression in vitro and in vivo. PG - 73-83 LID - 10.1021/bm201157f [doi] AB - Use of cationic polymers as nonviral gene vectors has several limitations such as low transfection efficiency, high toxicity, and inactivation by serum. In this study, varying amounts of low molecular weight branched polyethylenimine 1.8 kDa (bPEI 1.8) were introduced on to a neutral polymer, poly(vinyl alcohol) (PVA), to bring in cationic charge on the resulting PVA-PEI (PP) nanocomposites. We rationalized that by introducing bPEI 1.8, buffering and condensation properties of the proposed nanocomposites would result in improved gene transfer capability. A series of PVA-PEI (PP) nanocomposites was synthesized using well-established epoxide chemistry and characterized by IR and NMR. Particle size of the PP/DNA complexes ranged between 120 to 135 nm, as determined by dynamic light scattering (DLS), and DNA retardation assay revealed efficient binding capability of PP nanocomposites to negatively charged nucleic acids. In vitro transfection of PP/DNA complexes in HEK293, HeLa, and CHO cells revealed that the best working formulation in the synthesized series, PP-3/DNA complex, displayed ~2-50-fold higher transfection efficiency than bPEIs (1.8 and 25 kDa) and commercial transfection reagents. More importantly, the PP/DNA complexes were stable over a period of time, along with their superior transfection efficiency in the presence of serum compared to serum-free conditions, retaining the nontoxic property of low molecular weight bPEI. The in vivo administration of PP-3/DNA complex in Balb/c mice showed maximum gene expression in their spleen. The study demonstrates the potential of PP nanocomposites as promising nonviral gene vectors for in vivo applications. FAU - Goyal, Ritu AU - Goyal R AD - CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi-110007, India. FAU - Tripathi, Sushil K AU - Tripathi SK FAU - Vazquez, Esther AU - Vazquez E FAU - Kumar, Pradeep AU - Kumar P FAU - Gupta, Kailash C AU - Gupta KC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111216 PL - United States TA - Biomacromolecules JT - Biomacromolecules JID - 100892849 RN - 9002-89-5 (Polyvinyl Alcohol) RN - 9002-98-6 (Polyethyleneimine) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - CHO Cells MH - Cricetinae MH - Cricetulus MH - *DNA/chemistry/pharmacology MH - *Gene Expression MH - *Gene Transfer Techniques MH - Genetic Vectors/chemistry/pharmacology MH - HEK293 Cells MH - HeLa Cells MH - Humans MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Nanocomposites/*chemistry MH - *Polyethyleneimine/chemistry/pharmacology MH - *Polyvinyl Alcohol/chemistry/pharmacology EDAT- 2011/12/08 06:00 MHDA- 2012/04/25 06:00 CRDT- 2011/12/08 06:00 PHST- 2011/12/08 06:00 [entrez] PHST- 2011/12/08 06:00 [pubmed] PHST- 2012/04/25 06:00 [medline] AID - 10.1021/bm201157f [doi] PST - ppublish SO - Biomacromolecules. 2012 Jan 9;13(1):73-83. doi: 10.1021/bm201157f. Epub 2011 Dec 16.