: improve of chitosan mediated gene delivery system with retinoic acid and pectin for gene delivery to HepG2 has been investigated in the current dissertation. Initially, tragacntic acid (TA) -kind of pectin- was extracted from gum tragacanth. Molecular weight (MW) was determined by gel permeation chromatography and intrinsic viscosity. Desertification degree (ED) was measured by titration. Its cytotoxicity has been checked on Hela, HepG2 and L929. Chitosan-tragacanthic acid nanopartilces have been fabricated with ionic gelation method in different weight ratios. Chitosan-retinoic acid (RA) derivatives were prepared in various molar ratios via condensation method, and the validity of reaction was confirmed using FTIR and NMR spectroscopy. Micelles have been prepared with ultrasonic method. Critical concentration of micelle (CMC) was determined using pyrene. Loading of RA in the micelles was assayed, and loading efficacy, loading content and release rate were investigated using UV spectroscopy. Plasmid has been loaded on chitosan-TA nanoparticles and chotosan-RA micelles and in polyplexes by ionic gelation. Pectin has been coated on polyethylenimine (PEI) polyplex with same method in different weight ratios. Optimized charge ratio of vehicle to plasmid was determined through either gel electrophoresis or Cybergreen-1 fluorometry assay, and transfection was studied in charge ratios upper than optimum charge ratio. Particle size, surface charge and pH effect on surface charge and particle size of nanoparticles have been determined by light scattering method. Morphology was investigated by SEM. Finally, cytotoxicity of optimum particles were evaluated on Hela and HepG2 cell lines by MTT assay. MW and ED of TA were 300 kDa and 94%, respectively. TA had shown no cytotoxicity on mentioned cell lines, and its cell adhesion was better than alginate. Nano-composites of chitosan-tragacanthic acid were consisted of spherical particles with particle size blow than 200 nm with positive charge. Nanoparticles with weight ratio of 3, particle size of 132.5 ± 6.77 nm and charge ratio of 30.45 ± 1.84 mV were chosen for gene delivery study. Spherical micelles with CMC of 1.3×10 -2 to 2.13×10 -2 mg/ml were prepared. Their size and surface charge were reneged from 142.14 to 208.4 nm and from +27.25 to +34.48 mv, respectively. Gel electrophoresis results showed complete plasmid loading by nanoplexes in upper charge ratios comparing to chitosan polyplexes while it happened in lower charge ratio for miceplexes. Transfection of nanoplexes was higher than polyplexes in Hela and HepG2 cell lines. It can be attributed to galactose groups in side chain of TA and existing of asialoglicoprotein receptors in HepG2 cell membrane. Miceplexes gene expression was lower in Hela and HepG2 compared to that of polyplexes and nanoplexes. However, transfection was increased in presence of 10% fetal bovine serum. Plasmid content was more in this system comparing to other systems. Effect of pectin coat on cytotoxicity and stability of PEI polyplexes showed less cell cytotoxicity and more system stability comparing to uncoated polyplexes, while coated system transfection was not that much lower comparing to uncoated system. Overall, nanoplex is a proper choice for liver gene delivery because of targeting to hepatocytes. More stability of miceplex and its more gene expression in serum medium make this system more suitable for in vivo gene delivery. Pectin coat is a good method for gene delivery in in vivo because of less cell cytotoxicity and more system stability to glycosaminoglycan. Key worlds: chitosan, retinoic acid, pectin, tragacanthic acid, gene delivery, cytotoxicity