Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids

Alfei, Silvana; Taptue, Gaby Brice; Catena, Silvia; Bisio, Angela

doi:10.1007/s10118-018-2124-9

Cited by 22 publications

(35 citation statements)

References 92 publications

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“…To complete the characterization of the prepared cationic dendrimers, having further confirmation of their composition on the periphery and to determine their molecular weight without having to resort to routine well‐known but very expensive techniques like matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry, the titration of amine hydrochlorides with HClO 4 solutions in AcOH in the presence of mercuric acetate and quinaldine red as indicator proved simple and affordable. The accuracy of this method, already adopted by us to determine the molecular weight of cationic amino acid‐modified dendrimers previously prepared was secured by a sharp endpoint of titration, while its reliability has been demonstrated by the reproducibility of the results. Table shows the estimated peripheral composition of each prepared dendrimer, the N value and the molecular weight estimated by NMR spectra compared with the observed experimental values obtained from volumetric titration ( N (degree of freedom) = 5).…”

Section: Resultsmentioning

confidence: 99%

“…One of our recent papers described the preparation of seven biodegradable and non‐cytotoxic polyester‐based hydrophilic arginine dendrimers of fourth and fifth generation. Subsequently, six of them were successful in physically entrapping a mixture of ursolic and oleanolic acids, two non‐water‐soluble triterpene weak acids very common in the plant kingdom and extracted, in our case, from Salvia officinalis , achieving water‐soluble, in vivo administrable dendriplexes.…”

Section: Introductionmentioning

confidence: 93%

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

Alfei

Catena

2018

Polymer International

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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

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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

Alfei

Catena

2018

Polymer International

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“…They succeeded in physically entrapping two triterpenoids acids from plants kingdom endowed with several pharmacological properties hardly exploitable because of their low bioavailability and poor water solubility providing highly water-soluble prodrugs very promising for clinical applications of triterpenoids medical properties. 60 For an effective gene or drug transfection, an adequate residence time is requested so that a good delivery system should be able to preserve transported material from lysosome attack escaping from the endosome as soon as possible. 61 This can be realized causing the rupture of the endosome itself, and to do it the dendriplex must behave as a "proton sponge".…”

Section: Introductionmentioning

confidence: 87%

“…The accuracy of this method, already adopted by us to determine molecular weight of cationic amino acids-modified dendrimers previously prepared, 59,60,63 was secured by a sharp endpoint of titration, while its reliability has been demonstrated by the reproducibility of results. Table 2 shows the estimated peripheral composition of dendrimers prepared, the N value, and the molecular weight estimated by NMR spectra compared with the experimental one obtained from volumetric titrations [N (degree of freedom) = 5].…”

Section: Volumetric Titration Of Dendrimers 9 and 10mentioning

confidence: 99%

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

Alfei

Catena

2018

Polymers for Advanced Techs

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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.

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“…Highly hydrophobic drugs incorporated into polycationic dendrimers through physical through electrostatic interactions and hydrogen bonding can be obtained. Pentacyclic triterpenoid acids encapsulated into the G4, and G5 amino acids-modified PAMAM dendrimers have been prepared and solubilized, allowing a better bioavailability, and an increased pharmacokinetic [79]. The different interactions present between dendrimers and drugs, namely electrostatic interactions, dispersion forces, hydrophobic interactions, or hydrogen bonds among others, can ensure the formation of complexes.…”

Section: Physicochemical Propertiesmentioning

confidence: 99%

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Sandoval-Yáñez

Rodríguez

2020

Materials

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Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to the target tissue, drugs bioavailability, and controlled release. This review describes the latter approaches on the transport of bioactive molecules based on dendrimers. The review focus is on the last therapeutic strategies addressed by dendrimers conjugated with bioactive molecules. A brief review of the latest studies in therapies against cancer and cardiovascular diseases, as well as future projections in the area, are addressed.

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Synthesis of Water-soluble, Polyester-based Dendrimer Prodrugs for Exploiting Therapeutic Properties of Two Triterpenoid Acids

Cited by 22 publications

References 92 publications

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

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

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

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

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