A Biocompatible Arginine‐Based Polycation

Abstract

Self assembly between cations and anions is ubiquitous throughout nature. Important biological structures such as chromatin often use polyvalent assembly between a polycation and a polyaninon. Biomedical importance of synthetic polycations arises from their affinity to polyanions such as nucleic acid and heparan sulfate. However, the limited biocompatibility of synthetic polycations hampers the realization of their immense potential. By examining biocompatible cationic peptides, we hypothesize that a biocompatible polycation should be biodegradable and made from endogenous cations. We designed an arginine-based biodegradable polycation and demonstrated that it was orders of magnitude more compatible than conventional polycations in vitro and in vivo. This biocompatibility diminishes when L-arginine is substituted with D-arginine or when the biodegradable ester linker changes to a biostable ether linker. We believe this design can lead to many biocompatible polycations that can significantly advance a wide range of applications including controlled release, tissue engineering, biosensing, and medical devices.

Lysine-based polycation:heparin coacervate for controlled protein delivery

“…The total release after 21 days ranged from 17.4% to 58.8% for the −10 and 0 mV coacervates, respectively, with the −5 mV coacervate displaying an intermediate total release. We expect that multiple mechanisms play a role in the release of biomolecules: degradation of the polycation, as has been demonstrated with PEAD and similar polycations [17,30], dissociation of the coacervate in an ionic environment, and competition for heparin between the polycation and heparin-binding proteins. The dependence of release on charge supports the participation of the last mechanism.…”

Coacervate delivery systems for proteins and small molecule drugs

“…The strong, specific interaction between heparin and heparin-binding proteins results in very high loading efficiency of this coacervate, often greater than 99%. The release rate is influenced by multiple factors, including the heparin-binding affinity of the protein of interest, the net charge of the coacervate, and the polycation molecular weight, charge density, and biodegradation rate [18,19]. …”

“…One significant advantage of this coacervate system is owed to pre-conjugation of the growth factors to heparin which potentiates their bioactivities by mimicking the way that ECM proteoglycans present these factors to cell receptors [18,19]. In one instance, a single injection of heparin-based coacervate delivering fibroblast growth factor-2 (FGF-2) induced stable angiogenesis subcutaneously [20]; a similar benefit was observed after injection into the infarcted myocardium which resulted in improved cardiac function [21].…”

Polyoxometalate‐Driven Self‐Assembly of Short Peptides into Multivalent Nanofibers with Enhanced Antibacterial Activity

“…[1][2][3][4][5] These natural systems have inspired the development of many multivalent nanostructures with positively charged surfaces as artificial platforms for recognition, catalysis,g ene delivery, and antibacterial therapy. [1][2][3][4][5] These natural systems have inspired the development of many multivalent nanostructures with positively charged surfaces as artificial platforms for recognition, catalysis,g ene delivery, and antibacterial therapy.…”