New Ionic bis‐MPA and PAMAM Dendrimers: A Study of Their Biocompatibility and DNA‐Complexation

Abstract

Herein, the synthesis of five novel ionic dendrimers and their evaluation as biological carriers is reported. The compounds include an ionic bis-MPA dendrimer and four PAMAM dendrimers of different generations decorated with negatively charged hydrophilic chains of 2-[2-(2-methoxyethoxy)ethoxy]acetic acid as counter ions in order to increase their biocompatibility. The ionic dendrimers derived from bis-MPA have a low cytotoxicity at 0.5 mg · mL(-1) against U251MG and are even less toxic against mesenchymal stem cells; however, the PAMAM derivatives show high cytotoxicity at the same concentration. The five compounds are able to form complexes with plasmid DNA at different N/P ratios. The cytotoxicity and complexation ability of the new dendrimers were also compared with jetPEI, a linear polyethylenimine derivative commercially available as transfection reagent. The results indicate that the cytotoxicity of the ionic PAMAM dendrimers remains as an important drawback, whereas the ionic I-bis-MPA compound exhibits a high ability to complex pDNA and very low toxicity compared with jetPEI.

Nanoobjects formed by ionic PAMAM dendrimers: hydrophilic/lipophilic modulation and encapsulation properties

“…A similar approach was used later by Frey et al using a hyperbranched PEI polymer functionalized with dodecanoic or hexadecanoic acid. 28 The main aim of the work reported here is the development of ionic dendrimers interesting in Nanomedicine as drug-delivery systems, as well as in Materials Science, as self-organised liquid crystalline materials. 20 Indeed, liquid crystal dendrimers (LCDs) present an attractive option to design functional materials.…”

A study on the hemocompatibility of dendronized chitosan derivatives in red blood cells

“…Such undesirable effects may be attenuated by shielding the PAMAM dendrimer surface with polymers that reduce the charges, and modifications of PAMAM dendrimers represent an easy approach to improve their biocompatibility. For example, conjugation or hybrid formation with N -maleyl chitosan, 13 , 14 carboxymethyl chitosan, 69 , 78 chitosan, 79 zwitterionic chitosan, 68 arginine, 33 , 80 carboxybetaine acrylamide, 81 PEGylation, 36 2-[2-(2-methoxyethoxy)ethoxy]acetic acid, 35 gold nanoparticles, 82 oleic acid-functionalized graphene, 83 or quantum dots 84 , 85 has been used to improve the efficacy of drug/gene delivery and reduce the cytotoxicity.…”

“…In the past years, cationic PAMAM dendrimers have been reported to improve the solubility of low-aqueous-soluble drugs and condense plasmid DNA or small interfering RNA and demonstrated successful delivery of DNA into the target cells. 26 – 35 However, PAMAM dendrimers bearing amino terminals could cause certain cytotoxicity toward epithelial cells, endothelial cells, neurons, leukocytes, platelets, and red blood cells (RBCs). 13 , 34 , 36 – 38 In particular, the RBC toxicity of PAMAM dendrimers has attracted attention due to safety concerns regarding hemolysis.…”

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

“…27 In the area of NA delivery these are restricted to very few examples with amineterminated bis-HMPA [2,2-bis(hydroxymethyl)propanoic acid] dendrons for the encapsulation of DNA, largely described by Smith and coworkers. [37][38][39][40][41] The challenge associated to combine in the same structure unprotected primary/secondary amine groups -needed to get the cationic charge to complex NAs -with hydrolyzable (and so, electrophilic) bonds adds extra struggle to the already difficult task of engineering biodegradable dendritic vectors.…”