Antiviral and antibacterial potential of electrosprayed PVA/PLGA nanoparticles loaded with chlorogenic acid for the management of coronavirus and Pseudomonas aeruginosa lung infection.

Respiratory tract infections are a common cause of morbidity and mortality globally. The current paper aims to treat this respiratory disorder. Therefore, we elucidated the phytochemical profile of Euphorbia milii flowers and isolated chlorogenic acid (CGA) for the first time. The electrospraying technique was utilized to prepare CGA nanoparticles in polyvinyl alcohol (PVA)/PLGA polymeric matrix. Complete in vitro characterizations were performed to determine particle size, polydispersity index (PDI), zeta potential, loading efficiency (LE), scanning electron microscopy and in vitro release study. The optimum formula (F2) with a particle size (454.36 ± 36.74 nm), a surface charge (-4.56 ± 0.84 mV), % of LE (80.23 ± 5.74), an initial burst (29.46 ± 4.79) and % cumulative release (97.42 ± 4.72) were chosen for further activities. In the murine lung infection model, PVA/PLGA NPs loaded with CGA (F2) demonstrated in vivo antibacterial activity against Pseudomonas aeruginosa. Using a plaque assay, the in vitro antiviral activity was investigated. The F2 exhibited antiviral activity against coronavirus (HCoV-229E) and (Middle East respiratory syndrome coronavirus (MERS-CoV), NRCEHKU270). The IC50 of F2 against HCoV-229E and MERS-CoV was 170 ± 1.1 and 223 ± 0.88 µg/mL, respectively. The values of IC50 of F2 were significantly lower (p < .05) than that of free CGA. Therefore, the encapsulation of CGA into electrospray PVA/PLGA NPs would be a promising tool as an antimicrobial agent.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment.

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.

A nanotechnological approach in the current therapy of COVID-19: model drug oseltamivir-phosphate loaded PLGA nanoparticles targeted with spike protein binder peptide of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is today's most serious epidemic disease threatening the human race. The initial therapeutic approach of SARS-CoV-2 disease is based upon the binding the receptor-binding site of the spike protein to the host cell's ACE-2 receptor on the plasma membrane. In this study, it is aimed to develop a biocompatible and biodegradable polymeric drug delivery system that is targeted to the relevant receptor binding site and provides controlled drug release. Oseltamivir phosphate (OP) is an orally administered antiviral prodrug for primary therapy of the disease in biochemically activated carboxylate form (oseltamivir carboxylate OC). In the presented study, model drug OP loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) targeted with spike-binding peptide 1 (SBP1) of SARS-CoV-2 were designed to be used as an efficient and prolonged released antiviral drug delivery system. RY, EE, and DL values of the OP-loaded NPs produced by the solvent evaporation method were calculated to be 59.3%, 61.4%, and 26.9%, respectively. The particle size of OP-loaded NPs and OP-loaded NPs targeted with SBP1 peptide were 162.0 ± 11.0 and 226.9 ± 21.4 nm, respectively. While the zeta potential of the produced OP-loaded NPs was achieved negatively -23.9 ± 1.21 mV), the result of the modification with SBP1 peptide this value approached zero as -4.59 ± 0.728 mV. Morphological features of the OP-loaded NPs were evaluated using FEG-SEM. The further characterization and surface modification of the NPs were analyzed by FT-IR.In-vitrorelease studies of NPs showed that sustained release of OP occurred for two months that fitting the Higuchi kinetic model. By evaluating these outputs, it was reported that surface modification of OP-loaded NPs was significantly effective on characteristics such as size, zeta potential values, surface functionality, and release behavior. The therapeutic model drug-loaded polymeric formulation targeted with a specific peptide may serve as an alternative to more effective and controlled release pharmaceuticals in the treatment of COVID-19 upon an extensive investigation.

Self-assembled chromogen-loaded polymeric cocoon for respiratory virus detection.

Inspired by the self-assembly approach, in this work, the chromogen, 3,3',5,5'-tetramethylbenzidine (TMB), was successfully co-precipitated in aqueous solution to form collective nanoparticles (NPs) of signal molecules (TMB-NPs). Utilizing poly(lactide-co-glycolide) (PLGA) in the molecular delivery approach, the formed emulsion nanovesicle (TMB-NPs@PLGA) exhibits an enrichment of the collective signal molecules in a single antibody-antigen conjugation. A specific antibody-conjugated TMB-NPs@PLGA forms an immunocomplex sandwich structure upon the addition of influenza virus (IV)/A. The addition of dimethyl sulfoxide (DMSO) dissolves the PLGA nanovesicles, releasing the encapsulated TMB-NPs. Sequentially, the TMB-NPs release TMB molecules upon the addition of DMSO. The released TMB is catalytically oxidized by H2O2 with self-assembled protein-inorganic nanoflowers, where copper nanoflowers (CuNFs) acted as the nanozyme. The developed immunoassay demonstrates high sensitivity for IV/A with a limit of detection (LOD) as low as 32.37 fg mL-1 and 54.97 fg mL-1 in buffer and serum, respectively. For practical needs, a clinically isolated IV/A/H3N2 and spike protein of SARS-CoV-2 were detected with the LODs of 17 pfu mL-1 and 143 fg mL-1, respectively. These results show the applicability of the advanced TMB-NPs@PLGA-based colorimetric sensor for the highly sensitive detection of airborne respiratory viruses.

Structure-aided ACEI-capped remdesivir-loaded novel PLGA nanoparticles: toward a computational simulation design for anti-SARS-CoV-2 therapy.

The sudden arrival of novel coronavirus disease 2019 (COVID-19) has stunned the world with its rapidly spreading virus. Remdesivir, a broad spectrum anti-viral drug, is now under in vitro and in vivo investigation as a potential agent against SARS-CoV-2. However, the results of this therapy were recently equivocal due to no significant benefit in the clinical trial. Herein, combination molecular docking with dissipative particle dynamics (DPD) simulations is used to theoretically design angiotensin-converting enzyme inhibitor (ACEI)-containing remdesivir-loaded PLGA nanoparticles (NPs) for anti-SARS-CoV-2 therapy. Based on the therapeutic and lung protective effect of ACEI, the classical lisinopril molecule covalently grafted onto PLGA (L-PLGA) has been used to encapsulate remdesivir. A binding model is used to confirm the interactions between lisinopril and ACE on the surface of cells, as well as remdesivir and its intracellular targeting protein (RNA-dependent RNA polymerase (RdRp)). Furthermore, DPD simulations are applied to study the nano-aggregation of drug-free L-PLGA, and remdesivir loaded in L-PLGA. The lisinopril molecules were directly demonstrated to be on the surface of L-PLGA NPs. Molecular docking proved that hydrogen bonding was decisive for the encapsulation of remdesivir. With an increase in concentration, remdesivir loaded L-PLGA formed spherical NPs, and then underwent precipitation. Similar to the above conditions, high remdesivir loading was also observed to cause precipitation formation. Thus, the optimized remdesivir NPs in our study give insights into a rational platform for formulation design against this global pandemic.