Exploring the applications of hyaluronic acid-based nanoparticles for diagnosis and treatment of bacterial infections

Abstract

Hyaluronic acid (HA) has become a topic of significant interest in drug delivery research due to its excellent properties, including biosafety, biodegradability, and nonimmunogenicity. Moreover, due to its ease of modification, HA can be used to prepare several HA-based nanosystems using various approaches. These approaches involve conjugating/grafting of hydrophobic moieties, polyelectrolytes complexation with cationic polymers, or surface modification of various nanoparticles using HA. These nanoparticles are able to selectively deliver antibacterial drugs or diagnostic molecules into the site of infections. In addition, HA can bind with overexpressed cluster of differentiation 44 (CD44) receptors in macrophages and also can be degraded by a family of enzymes called hyaluronidase (HAase) to release drugs or molecules. By binding with these receptors or being degraded at the infection site by HAase, HA-based nanoparticles allow enhanced and targeted antibacterial delivery. Herein, we present a comprehensive and up-to-date review that highlights various techniques of preparation of HA-based nanoparticles that have been reported in the literature. Furthermore, we also discuss and critically analyze numerous types of HA-based nanoparticles that have been employed in antibacterial delivery to date. This article offers a critical overview of the potential of HA-based nanoparticles to overcome the challenges of conventional antibiotics in the treatment of bacterial infections. Moreover, this review identifies further avenues of research for developing multifunctional and biomimetic HA-based nanoparticles for the treatment, prevention, and/or detection of pathogenic bacteria. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Keywords: bacterial infection; drug conjugate; hyaluronic acid; surface modification; targeted nano-drug delivery.

FIGURE 1

The structure of HA as well as potential locations for chemical modification of the polymer

FIGURE 2

Nano‐delivery systems based on HA. Both (a) and (b) illustrate conjugation of HA with a hydrophobic moiety or drug, which self‐assemble into NPs; (c) ionic gelation of HA with cationic polymer; and (d) HA‐coated NP

FIGURE 3

The total number of publications on HA‐based NPs. When the terms “hyaluronic acid” and “nanoparticles” were entered in PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) and Scopus (https://www.scopus.com/search), the number of publications that appeared year after year was graphed

FIGURE 4

Schematic illustration of LVF‐NGs for targeting intracellular infections (Montanari et al., 2014)

FIGURE 5

Head‐to‐head comparison of HA‐NGs and coated poly (lactic‐co‐glycolic acid) NPs for AZ delivery (Kłodzińska, Rahanjam, et al., 2019)

FIGURE 6

Schematic illustration of LLKKK18‐loaded HA‐NGs targeting intracellular mycobacteria (Silva et al., 2016)

FIGURE 7

Schematic representation of antibiofilm peptide, DJK‐5, loaded into HA‐NGs (Kłodzińska, Rahanjam, et al., 2019)

FIGURE 8

Scheme illustrating the ionic complexation of LAE‐HA and its antibacterial activity (Gamarra et al., 2018)

FIGURE 9

Scheme illustrating formulation of HA‐OLA polymersomes to eradicate MRSA infection (Walvekar et al., 2019)

FIGURE 10

Schematic illustration of (a) tetracycline‐loaded HA‐ZIF8 and (b) VCM‐loaded HA‐ZIF8 targeting intracellular bacteria (Liu et al., ; X. Zhang et al., 2019)

FIGURE 11

Schematic representation of (a) layer‐by‐layer coating of MSN‐Lys‐HA‐PGMA and the possible antibacterial mechanism for each layer. (b) Synthesis of an “on‐demand” integrated Ab@S‐HA@MMSNs for diagnosis and treatment toward S. aureus (Wu et al., ; Xu et al., 2019)

FIGURE 12

Schematic illustration of rapamycin‐loaded HA‐based micelles (Qiu et al., 2019)

FIGURE 13

Hyaluronic acid‐based nanoparticles (right) that have been developed for the detection and/or eradication of various bacteria (left) over the last two decades