Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positively charged amino acids

Abstract

Dendrimers are nanostructured ‘architectural motifs’ with a well‐tailored polymeric structure, symmetric tree‐like shape and the presence of several functional groups and inner cavities, and are of eminent interest in many biomedical applications such as drug delivery, gene transfection and imaging. In the work reported, reliable protocols for the synthesis of polyester‐based, hydrolysable, amphiphilic polycationic dendrimers were developed. A C‐18 hydrocarbon chain provided by a biocompatible fatty acid, stearic acid, and second‐ and third‐generation dendrons based on 2,2‐bis(hydroxymethyl)propionic acid were built on 2,2‐bis(hydroxymethyl)propanol and pentaerythritol as core molecules. αN‐BOC‐ω'N‐(NO2)‐l‐arginine alone, mixed with αN,ϵN‐di‐BOC‐l‐lysine or also with N,N′‐dimethylglycine and αN‐BOC‐methylglycine were successfully bound to the prepared polyester neutral scaffolds and, after the removal of protecting groups, five cationic dendrimers were obtained. Their structure was confirmed using NMR analysis and experimental molecular weight. Their buffer capacity, comparable to that of polyethyleneimines, was optimal, high viability percentage values were obtained from cytotoxicity assays and zeta potential and mean particle size were in the desired ranges. The synthesized nanostructured compounds that harmonize a multifunctional polycationic shell, a biodegradable uncharged polyester matrix and a C‐18 hydrophobic portion helpful for an improved hydrophilic–lipophilic balance in their structure embody all the fundamental features to be suitable for biomedical applications. © 2018 Society of Chemical Industry

From Nanobiotechnology, Positively Charged Biomimetic Dendrimers as Novel Antibacterial Agents: A Review

“…Despite being considered very attractive for biomedical applications because of their lower density of cationic charge when compared to PAMAM Ds, PEI-Ds, and PPI Ds, generally associated with low cytotoxicity [ 92 , 93 , 94 , 95 ], only very recently uncharged dendrimer matrices, decorated with amino acid residues, were considered to be less toxic antimicrobial alternatives. Within this category, peripherally amino acid-modified, polyester-based dendrimer scaffolds, obtained starting from 2,2- bis (hydroxymethyl)propanoic acid ( bis -HMPA), as AB2 monomer, have several features that make them particularly suitable as novel antimicrobial agents.…”

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

“…The functionalization of the end-groups in the outer surface of dendrimers with different functional groups modify their physicochemical properties and biological behaviors [68,69]. Recently, dendrimers decorated with positively charged amino acids on the superficial were synthesized [70]. Recently, Govender et al [71] formulated and evaluated novel pH-responsive lipid-dendrimer hybrid nanoparticles for the targeted delivery of vancomycin in the site infection.…”

Telodendrimers: Promising Architectural Polymers for Drug Delivery

“…One of the very interesting recent additions to the area of dendrimers is the polyester-based hyperbranched macromolecules, reported by Alfei’s group [ 99 , 100 , 101 , 102 ]. This elegant and versatile set of macromolecules ( Figure 2 ) are intriguing alternatives to heavily utilized PAMAM dendrimers, with ease of tunable surface functionalization with a variety of functional groups, leading to neutral and charged nanostructures with low toxicities.…”

“…This elegant and versatile set of macromolecules ( Figure 2 ) are intriguing alternatives to heavily utilized PAMAM dendrimers, with ease of tunable surface functionalization with a variety of functional groups, leading to neutral and charged nanostructures with low toxicities. These biocompatible scaffolds are promising candidates for applications in biology, as demonstrated by their potential in a series of therapeutic evaluations [ 99 , 100 , 101 , 102 , 103 , 104 , 105 ]. Such a structural outline, i.e., a dendron with an alkyl chain at the focal point, was previously reported by Newkome et al [ 30 ], and investigated for its ability to form micelle structures.…”

“… Polyester-based macromolecules reported by Alfei’s group: ( A ) [ 99 ]; in ( B ) (suffix M in the terminal moieties = l -arginine; L = l -lysine, S = sarcosine) [ 103 ]. …”