Zinc-stabilized colloidal polyelectrolyte complexes of chitosan/hyaluronan: a tool for the inhibition of HIV-1 infection

Abstract

International audienceZinc(II) stabilized polyelectrolyte nano-complexes (PECs) of chitosan and hyaluronan (HYA) were designed as safe and efficient drug delivery systems. HIV-1 reverse transcriptase inhibitor tenofovir (TF) was quantitatively encapsulated and the particle interface could be functionalized in PBS with targeting proteins such as anti-alpha 4b7 immunoglobulin A. Chitosan-HYA nanoPECs were non-cytotoxic on human peripheral blood mononuclear cells (PBMCs), within the investigated nanoparticle concentrations. A dose-dependent reduction of the HIV-1 infection of PBMCs co-cultured with the nanocarriers was observed. Even more interestingly, a synergistic effect was evidenced with the nanocarriers by comparing the IC50 (50% inhibitory concentration) value of the aqueous TF solution (4.35 mu mol L-1) with that of TF loaded nanoPECs (1.71 mu mol L-1) and anti-a4b7 IgA functionalized TF/nanoPECs (1.01 mu mol L-1). This effect could be attributed to the presence of zinc(II) in the formulation of the colloids. All these data establish that the zinc(II) stabilized chitosan-HYA nanoPECs can be potentially efficient and safe colloidal delivery system candidates for enhancing antiviral activities in the treatment of HIV infection and AIDS

New Advances in Nanomaterial‐Based Antiviral Strategies

“…The resulting nanocomposite system can target HIV‐enriched human peripheral blood mononuclear cells (PBMCs) with reduced drug toxicity, thereby preventing PBMCs from HIV infection. [ 79 ]…”

“…The resulting nanocomposite system can target HIVenriched human peripheral blood mononuclear cells (PBMCs) with reduced drug toxicity, thereby preventing PBMCs from HIV infection. [79] Inorganic nanomaterials such as mesoporous silica NPs (MSNs) have also been widely used in drug delivery due to their excellent biological safety, high drug loading efficiency, and easy preparation and modification. Amino-functionalized MSNs loaded with drugs of shikimic acid or quercetin can kill pathogenic avian influenza H5N1 virus and showed anti-inflammatory effects additionally.…”

“…[89] Once a healthy vaccinated individual is exposed to viral pathogens, pre-produced antibodies in vivo recognize and neutralize viruses before host cells get infected. Compared to innate immunity, pre-existing antibodies produced PHEA-EDA-DPPE-GAL NPs [134] PLGA nanospheres Acyclovir HSV Sustained release, improved oral bioavailability [74] PLGA NPs Bictegravir HIV-1 Sustained release, reduced cytotoxicity and dosing [135] Combination antiretroviral drugs [136] PETIM dendrimers siRNA HCV Targeted specific delivery, decreased systemic toxicity [72] Cationic nanogels Azidothymidine HIV-1 Increased site-specific delivery, decreased systemic toxicity [76] Hydroxypropyl-β-cyclodextrin Acyclovir HSV, varicella-zoster virus Improved solubility and oral bioavailability [137] Carboxylated cyclodextrin-based nanosponges HSV-1 Sustained release, improved solubility and biocompatibility [138] β-cyclodextrin GCV Human cytomegalovirus Improved bioavailability, decreased toxicity [139] Chitosan nanospheres Acyclovir HSV Increased site-specific delivery, prolonged release [75] Zn(II) stabilized chitosan-HYA nanoPECs Tenofovir HIV Increased site-specific delivery, decreased systemic toxicity [79] Liposomes LL-37, indolicidin HSV-1 Improved stability, high encapsulation, decreased systemic toxicity [140] Niosomes Acyclovir HSV Improved stability, decreased systemic toxicity [141] Lipid NPs Atazanavir, ritonavir, tenofovir HIV Increased drug loading, long-acting targeted release, reduced doses [78] Amino-functionalized MSNs Shikimic acid, quercetin Avian influenza H5N1 virus Targeted release, improved antiviral effect [80] Gal-AMSNs shDNA HCV Targeted liver specificity, improved stability [81] LC-MSNs ML336 VEEV Increased stability and solubility, good biocompatibility [82] AuNPs Raltegravir HIV Improved bioavailability, blood-brain barrier penetrability [142] HA-AuNPs IFNα HCV Targeted liver specificity, increased stability, and circulation time in vivo [83] Pectin-reduced AuNPs Zidovudine HIV Targeted specificity, sustained release [143] AgNPs Oseltamivir Influenza H1N1 virus Decreased drug resistance, enhanced antiviral activity [144] Nanodiamond Efavirenz HIV-1 Increased drug stability, prolong drug circulation time, blood-brain barrier penetrability [84] Single-walled carbon nanotubes Ribavirin Grass carp reovirus Improved antiviral effect and bioav...…”

Smart polymeric eye gear: A possible preventive measure against ocular transmission of COVID-19

“…Wu et al prepared a polyelectrolyte complex of chitosan with hyaluronan and got the composite stabilized with zinc. The antiviral activity of the developed complex was increased against HIV, which could be attributed to their ability to block the entry point of HIV to the host cell [25] . Li et al prepared an ionic complex of chitosan with sialyloligosaccharides (SOS) and tested against influenza (H1N1) and found that a higher ratio of SOS results in increased adhesion, more cytoprotective and a potential anti-influenza agent [26] .…”

Development and Characterization of Antimicrobial Textiles from Chitosan-Based Compounds: Possible Biomaterials Against SARS-CoV-2 Viruses

“…Nevertheless, as it was mentioned above, CH as a native molecule has limited activity as an antimicrobial agent over a wide range of viruses, but substitution at the amino group and hydroxyl group can significantly alter its efficacy against various viral strains [18]. In fact, different CH derivatives have been reported to have potential as anti-HIV agents [19][20][21]. Gao et al have further demonstrated that 3, 6-O-sulfated chitosan was able to inhibit a broad spectrum of HPV pseudoviruses (HPV PV) [22].…”