title: Conjugation of poly(amidoamine) dendrimers with various acrylates for improved delivery of plasmid encoding interleukin-12 gene.
abstract: In this study, a small library of polyamidoamine (PAMAM) derivatives was prepared through the conjugation of its amines with various acrylates containing 5-21 carbon chain lengths at two different conjugation degrees, and the ability of the nano-sized PAMAM-based complexes to transfer the plasmid encoding interleukin-12 (IL-12) gene into the cells was studied. As the wide clinical application of the recombinant IL-12 protein has been limited due to several deaths reported following the systemic administration of the protein, local expression of the IL-12 gene inside the tumor target has been considered as an effective alternative strategy. The idea subjacent to this type of modification was to enhance transfection efficiency by the synergistic effects of endosome buffering via the PAMAM amines and the interaction with biological membranes caused by the hydrophobic moieties grafted on the PAMAM structure. Acrylate conjugation of primary amines on PAMAM structure enhanced transfection efficiency, with the highest level of IL-12 expression occurring with the conjugates containing five to nine carbon chains on their periphery at the grafting degree of 10%. The results obtained in this study suggest that combining the cationic nature of PAMAM along with modulating the hydrophobicity of the dendrimer to achieve an appropriate hydrophobic-hydrophilic balance yields the optimal carriers for non-viral gene delivery.
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sabahi
authors.affiliation: Department of Pharmaceutics, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Soliman Mohammadi
authors.initials: SM
authors.lastname: Samani
authors.affiliation: Department of Pharmaceutical Biotechnology, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Pharmaceutical Sciences Research Center, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran dehshahria@sums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Dehshahri
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018664:Interleukin-12 / Q000235:genetics*; D008422:Materials Testing; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D014162:Transfection / Q000379:methods*
chemical_list: D000179:Acrylates; D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D018664:Interleukin-12
keywords: Gene delivery; interleukin-12; nanoparticle; polyamidoamine