Hyaluronan/Tannic Acid Nanoparticles Via Catechol/Boronate Complexation as a Smart Antibacterial System

Abstract

Nanoparticles based on hyaluronic acid (HA) are designed to deliver tannic acid (TA) as an antimicrobial agent. The presence of HA makes these particles potentially useful to target bacteria that colonize cells presenting HA membrane receptors (e.g. CD44), such as macrophages. HA bearing 3-aminophenyl boronic acid groups (HA-APBA) is reacted with TA, yielding nanoparticles with a size that decreases with decreasing HA molecular weight (e.g. 200 nm for 44 kDa, 400 nm for 737 kDa). The boronate esters make the nanoparticles stable at physiological pH, but their hydrolysis in an acidic environment (pH = 5) leads to swelling/solubilization, therefore potentially allowing TA release in endosomal compartments. We have assessed the nanoparticle toxicity profile (on RAW 264.7 macrophages) and their antimicrobial activity (on E. coli and on both methicillin-sensitive and -resistant S. aureus). The antibacterial effect of HA-APBA/TA nanoparticles was significantly higher than that of TA alone, and has very similar activity to TA coformulated with a reducing agent (ascorbic acid), which indicates both the nanoparticles to protect TA catechols from oxidation, and the effective release of TA after nanoparticle internalization. Therefore, there is potential for these nanoparticles to be used in stable, effective, and potentially targetable nanoparticle-based antimicrobial formulations.

Using Artificial Skin Devices as Skin Replacements: Insights into Superficial Treatment

“…Experimental tests showed the efficacy of aSMAMPs toward Escherichia coli cells at pH 5.0. An alternative system prepared by Tirelli and co‐workers involves the encapsulation of tannic acid (TA) into hyaluronic acid (HA) nanoparticles for antimicrobial delivery purposes . The nanoparticles were capable of precisely targeting bacteria via specific HA interaction with cell surface receptors.…”

“…An alternative system prepared by Tirelli and co-workers involves the encapsulation of tannic acid (TA) into hyaluronic acid (HA) nanoparticles for antimicrobial delivery purposes. [92] The nanoparticles were capable of precisely targeting bacteria via specific HA interaction with cell surface receptors. pH-responsive crosslinks between HA and TA in the form of boronate esters conferred stability to the nanoparticles at physiological pH, but hydrolyzed at acidic pH, causing nanoparticles to swell and release TA into the endosomal areas.…”

Facile preparation of degradable multi-arm-star-branched waterborne polyurethane with bio-based tannic acid

“…This excellent DPPH radical scavenging activity is mainly attributed to the catechol groups of TA that can serve as electron donors and react with free radicals effectively to convert them into more stable products. 26,27 Hydroxyl radical scavenging assay. Hydroxyl radical, as the most toxic radical among the reactive oxygen species (ROS) and one of the most active radicals, can react with a range of substances in human body, thus leading to a variety of diseases.…”

Pursuing Intracellular Pathogens with Hyaluronan. From a ‘Pro-Infection’ Polymer to a Biomaterial for ‘Trojan Horse’ Systems

“…In the last decades, several kinds of HA-based nano-carriers have been developed, including self-assembling nanohydrogels (NHs) [ 71 , 72 , 73 ], covalently [ 74 , 75 ] or physically cross-linked nanoparticles, HA-coated liposomes [ 76 , 77 ] or inorganic nanoparticles [ 78 , 79 ] and bio-conjugates [ 80 , 81 ], and employed for a wide range of applications [ 82 , 83 ]. A number of stimuli-responsive HA nano-carriers have been also developed for the targeted and responsive delivery of therapeutics [ 84 , 85 ].…”

“…Therefore, several degradable linkages including di-sulfide [ 92 ] and other pH-sensitive derivatives [ 93 ], have been used to obtain chemically cross-linked stimuli-responsive nanoparticles. For example, HA-boronate derivative has been synthesised with the aim to develop pH-responsive and chemically cross-linked nanoparticles [ 85 ], by spontaneously forming boronate esters with polycatechols, by very mild conditions. The same strategy was also applied for the development of pH-responsive HA bio-conjugates with a number of diol/catechol-based therapeutics [ 81 ].…”