Facile Synthesis of Polyester Dendrimers as Drug Delivery Carriers

Abstract

Aliphatic polyester dendrimers are attractive carriers for in vivo delivery of bioactive molecules due to their biocompatibility and biodegradability, but efficient precision synthesis of these dendrimers without tedious purifications remains challenging. Herein, we report an efficient synthesis approach to polyester dendrimers from two AB2-type monomers via combining a click reaction of thiol/acrylate Michael addition with esterification. The reaction solution of each generation contains only the targeted dendrimer macromolecules; thus, the only required separation is simple precipitation. The resulting hydroxyl-terminated fifth-generation dendrimer is thermoresponsive with a LCST of 41 °C. The dendrimer could be further pegylated to obtain a water-soluble biocompatible dendrimer capable of encapsulation and controlled release of a hydrophobic anticancer drug, doxorubicin.

Polyester Dendrimers: Smart Carriers for Drug Delivery

“…This synthetic strategy is straightforward, but when the protection/deprotection reactions are incomplete, defects and thus polydispersity are introduced. Shen and coworkers [19] suggest that aliphatic polyester dendrimers without heterocyclics have better biocompatibility and biodegradability for translational nanocarriers. Using the highly efficient thiol/acrylate Michael addition reactions, a strategy for the synthesis of bis-HMPA-based dendrimers without any protection/deprotection steps was developed.…”

“…The IC 50 of the DOX in the G5-PEG/ DOX to SKOV-3 ovarian cancer cells was 0.085 μg/mL, not significant different from that of free DOX (0.056 μg/mL). Further evaluations of this type of dendrimers as drug carriers are currently underway [19]. Scheme 7.…”

“…Conventionally, nanoscale therapeutics is derived from polymer-drug conjugates, in which a drug is covalently bound through cleavable linkages such as the pH sensitive cis-aconityl, hydrazine, and acetal linkages [56,[90][91][92][93][94][95][96][97][98]. On the other hand, supramolecular drug delivery systems based on block copolymer micelles or dendritic systems have shown great promise and utility for tumor targeting and drug delivery [8,19,[99][100][101][102][103]. Both covalent and non-covalent systems can utilize the enhanced permeability and retention (EPR) phenomenon [9][10][11].…”

“…The success of dendritic nanoparticles for drug delivery applications largely depends on the ability of scientists to design smart carriers with the ability to overcome drug leakage, immunogenicity, cytotoxicity, reticuloendothelial system uptake, and hemolytic toxicity among other shortcomings. One strategy to overcome these shortcomings is to use polyester dendrimers which have been shown to be non-toxic and biocompatible [19,[56][57][58][59][60]. By attaching a drug to a suitable carrier, it is possible to enhance its aqueous solubility, increase its circulation half-life, target certain tissues, improve drug transit across biological barriers, and slow drug metabolism [61][62][63][64][65][66].…”

Polyolefin elastomer grafted unsaturated hindered phenol esters: synthesis and antioxidant behavior

“…Over the past decade, supramolecular architectures and dendritic macromolecules have gained interest in drug delivery, gene therapy and reacting with harmful substances due to precise control over structure and numerous possible sites for functionalization via covalent and non-covalent chemical groups. [21] Using dendrimer-like substances such as polyglycerols, phenolic acid-modified hyperbranched antioxidant compounds can be prepared. [22] In this study, we investigate the design and synthesis of novel esters of 3,5-di-tert-butyl-4-hydroxybenzoic acid and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid bearing unsaturated alcohol chains with various length and double bonds.…”