title: PAMAM-pullulan conjugates as targeted gene carriers for liver cell.
abstract: Targeted nano-carriers are highly needed to promote nucleic acid delivery into the specific cell for therapeutic approaches. Pullulan as a linear carbohydrate has an intrinsic liver targeting property interacting with asialoglycoprotein receptor (ASGPR) found on liver cells. In the present study, we developed polyamidoamine (PAMAM)-pullulan conjugates and investigated their targeting activity in delivering gene into liver cells. The particle size, zeta potential, buffering capacity and ethidium bromide exclusion assays of the conjugates were evaluated. The cytotoxicity and transfection efficiency of new derivatives were assessed following in vitro transfection of HepG2 (receptor positive) and N2A (receptor negative) cell lines. Size of conjugated polymers ranged between 118 and 184 nanometers and their cytotoxicity were similar to PAMAM. Among six produced nanocarriers, G4PU4 and G5PU4 enhanced transfection efficiency in HepG2 cells compared to unmodified PAMAM. Therefore, the PAMAM-pullulan derivatives seem to improve delivery of nucleic acids into the liver cells expressing asialoglycoprotein receptor with minimal transfection in non-targeted cells.
authors.affiliation: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Askarians891@mums.ac.ir.
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Askarian
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Abnouskh@mums.ac.ir.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Ayatollahis881@mums.ac.ir.
authors.forename: Sara
authors.initials: S
authors.lastname: Ayatollahi
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Amelfs1@mums.ac.ir.
authors.forename: Sara Amel
authors.initials: SA
authors.lastname: Farzad
authors.affiliation: Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Oskueekr@mums.ac.ir.
authors.forename: Reza Kazemi
authors.initials: RK
authors.lastname: Oskuee
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D005822:Genetic Vectors / Q000737:chemistry*; D005936:Glucans / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D014162:Transfection
chemical_list: D050091:Dendrimers; D005936:Glucans; C009109:pullulan
keywords: Gene delivery; Nanoparticle; PAMAM dendrimer; Pullulan