Lactose azocalixarene drug delivery system for the treatment of multidrug-resistant pseudomonas aeruginosa infected diabetic ulcer

Abstract

Diabetic wound is one of the most intractable chronic wounds that is prone to bacterial infection. Hypoxia is an important feature in its microenvironment. However, it is challenging for antimicrobial therapy to directly apply the existing hypoxia-responsive drug delivery systems due to the active targeting deficiency and the biofilm obstacle. Herein, we customizes a hypoxia-responsive carrier, lactose-modified azocalix[4]arene (LacAC4A) with the ability to actively target and inhibit biofilm. By loading ciprofloxacin (Cip), the resultant supramolecular nanoformulation Cip@LacAC4A demonstrates enhanced antibacterial efficacy resulting from both the increased drug accumulation and the controlled release at the site of infection. When applied on diabetic wounds together with multidrug-resistant Pseudomonas aeruginosa infection in vivo, Cip@LacAC4A induces definitely less inflammatory infiltration than free Cip, which translates into high wound healing performance. Importantly, such design principle provides a direction for developing antimicrobial drug delivery systems.

Triple targeting host–guest drug delivery system based on lactose-modified azocalix[4]arene for tumor ablation

“…LacAC4A is an amphiphilic compound (critical aggregation concentration = 8.0 μM), and can self-assemble into spherical-like nanoparticles. 64 Upon loading DOX, DOX@LacAC4A showed an average hydrated diameter of 75 ± 5 nm from dynamic light scattering (DLS) measurements (Fig. 1d), which was larger than that of free LacAC4A (25 nm).…”

“…1d), which was larger than that of free LacAC4A (25 nm). 64 Transmission electron microscopy (TEM) images of DOX@LacAC4A illustrated the irregular spherical-like morphology of around 70 nm (Fig. 1d inset and Fig.…”

“…The lactose groups not only improve the water solubility and biocompatibility, but more importantly, they impart the active targeting ability because of the interactions between lactose and the glycoproteins on the surface of cancer cells. 64 The amphiphilicity of LacAC4A facilitates the formation of the assembly, promoting the accumulation of LacAC4A nanoparticles in the tumor area by the EPR effect. Collectively, due to the features of tumors (leaky tumor vasculature and defective lymphatic drainage, 65 a hypoxia microenvironment, and overexpressed ASGP receptors), LacAC4A was well tailored to be a delivering vector that integrates all three target elements (passive, active and stimuli-responsive targeting capabilities) into one (Fig.…”

Recent Advances in Supramolecular-Macrocycle-Based Nanomaterials in Cancer Treatment

“…The lack of oxygen in the tumor site causes an imbalance in the redox state of the cancer cells [ 71 ]. Taking advantage of this property, Guo et al introduced azo groups into the upper rim of calixarenes and designed a series of hypoxia-responsive azocalixarenes [ 72 , 73 , 74 ]. For example, they reported a carboxylated azocalix(4)arene (CAC4A) for hypoxia-targeted drug delivery [ 75 ].…”

Recent nanotechnology-based strategies for interfering with the life cycle of bacterial biofilms

“…123 Based on overexpression of azoreductase by bacteria in the hypoxic biofilm microenvironment, Juan-Juan Li et al synthesized lactose-modified azocalix[4]arene (LacAC4A) and fabricated supramolecular nanoformulation using LacAC4A for hypoxia-responsive antibiotic delivery. 124…”