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

Abstract

Dendrimers are nanostructured “architectural motifs” which fascinate researchers for their several potentiality due to well‐tailored structure, symmetric tree‐like shape, and abilities in entrapping or binding hydrophilic or hydrophobic entities such as genetic materials, drugs, and target molecules. Nowadays dendrimers inhabit the top places among the materials suitable for biomedical applications as drug delivery, gene transfection, and imaging. In this work, we report the design and realization of two versatile successful procedures to decorate a fourth generation polyester‐based dendrimer matrix with a mixture of four different amino acids. The hydrochloride dendrimers achieved after removal of protecting groups were characterized by a core‐shell structure. They harmonized a not charged hydrolysable inner matrix potentially able to accommodate hydrophobic molecules and a cationic highly hydrophilic crown conferred by biocompatible amino acids that provided very satisfactory buffer capacity and will allow easy host/guest electrostatic interactions. Their structures and peripheral composition were confirmed by NMR analysis and experimental molecular weight computed by volumetric titration, while their buffer capacity was obtained by potentiometric titrations. Because in the inner matrix, the achieved hetero dendrimers do not present the high density of positive charges typical of PAMAM, they ensure a lower level of toxicity. But thanks to the cationic periphery, as preliminary investigations still in progress have already put in evidence, they were able to entrap not water soluble molecules by electrostatic interactions, with the result to increase their water solubility in a very satisfactory or amazing way. They therefore represent two new very promising devices for biomedical applications.

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.…”

“…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. These structures are characterized by good biodegradability, due to the easy physiological hydrolysis [ 92 , 93 , 94 , 95 ], a favorable hydrophilic lipophilic balance (HLB) due to the presence of an uncharged matrix and a cationic periphery, and can be esterified with a high number of amino acids, given the high multivalence of Ds. For these reasons, amino acid-modified polyester-based Ds could mimic synthetic dendrimer peptides which, as reported in the previous section, have provided remarkable results as antimicrobial agents, together with low levels of toxicity to eukaryotic cells.…”

Ring-opening polymerization of β-butyrolactone in the presence of alkali metal salts: investigation of initiation course and determination of polymers structure by MALDI-TOF mass spectrometry

“…Monopotassium salts of several carboxylic acids were prepared and applied for initiation of β-BL polymerization in order to obtain reactive polyfunctional polyesters [19][20][21]. The results of polymers analysis are presented in Table 3. 13 C NMR analysis of polymers prepared by use of monopotassium salt of malonic acid (14) or diglycolic acid (15) indicated very low content of transcrotonate end groups in the polymers.…”

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.…”