Synthesis and characterization of fourth generation polyester-based dendrimers with cationic amino acids-modified crown as promising water soluble biomedical devices

Dendrimers are nanostructured \u201carchitectural motifs\u201d which fascinate researchers fortheir several potentiality due to well\u2010tailored structure, symmetric tree\u2010like shape,and abilities in entrapping or binding hydrophilic or hydrophobic entities such asgenetic materials, drugs, and target molecules. Nowadays dendrimers inhabit thetop places among the materials suitable for biomedical applications as drug delivery,gene transfection, and imaging. In this work, we report the design and realization oftwo versatile successful procedures to decorate a fourth generation polyester\u2010baseddendrimer matrix with a mixture of four different amino acids. The hydrochloridedendrimers achieved after removal of protecting groups were characterized by acore\u2010shell structure. They harmonized a not charged hydrolysable inner matrixpotentially able to accommodate hydrophobic molecules and a cationic highlyhydrophilic crown conferred by biocompatible amino acids that provided very satis-factory buffer capacity and will allow easy host/guest electrostatic interactions.Their structures and peripheral composition were confirmed by NMR analysis andexperimental molecular weight computed by volumetric titration, while their buffercapacity was obtained by potentiometric titrations. Because in the inner matrix, theachieved hetero dendrimers do not present the high density of positive chargestypical of PAMAM, they ensure a lower level of toxicity. But thanks to the cationicperiphery, as preliminary investigations still in progress have already put in evidence, they were able to entrap not water soluble molecules by electrostatic inter-actions, with the result to increase their water solubility in a very satisfactory oramazing way. They therefore represent two new very promising devices for bio-medical applications

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

Dendrimers are nanostructured \u201carchitectural motifs\u201d with a well tailored polymeric structure, symmetric tree-like shape, the presence of several functional groups and inner cavities, and are of eminent interest in many biomedical applications as drug delivery, gene transfection and imaging. In this paper, 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 as 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. \u3b1N-BOC-\u3c9\u2019N-(NO2)-L-arginine alone, mixed with \u3b1N,\u3b5N-di-BOC-L-lysine or also with N,N\u2019-dimethylglycine and \u3b1N-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 by NMR analysis and experimental molecular weight. Their buffer capacity, comparable to that of PEIs, was optimal, high viability percentage values were obtained from cytotoxicity essays and zeta potential and mean particles size were in the desired range. 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