COVID-19 pandemic: Mechanistic approaches and gender vulnerabilities.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19), a severe respiratory damaging syndrome with serious health complications worldwide. SARS-CoV-2 was unfamilar before the epidemic started in Wuhan, China, in December 2019. COVID-19 is currently a pandemic influencing several countries worldwide. One of the mysteries of the new coronavirus is that it is deadlier for men than women with the male mortality rate is twice as high as that of females.

Fabrication and optimization of febuxostat-loaded chitosan nanocarriers for better pharmacokinetics profile.

The current research was planned to enhance the bioavailability of hydrophobic drug after oral administration through the development of a nanoparticle drug delivery system (DDS). Therefore, febuxostat-loaded chitosan nanoparticles (FLC NPs) were prepared using a modified ionic gelation method and optimized the reaction conditions through the design of experiments. Design expert software was used to check the desirability of the central composite design and the interactive effects of the independent variables (chitosan concentration, ratio of chitosan to linker, and pH of the medium) on the response variables (size distribution, zeta potential, polydispersity index (PDI), and entrapment efficiency (EE)) of FLC NPs. All ingredients of the optimized formulation (formulation Q) were compatible with each other as evident from FTIR, PXRD, and TGA studies, and displayed 234.7 nm particle size, 0.158 PDI, 25.8 mV zeta potential, and 76.9 % EE. TEM, SEM, and AFM exhibited a smooth, dense, and uniform structure without any visible pores in the structure of FLC NPs. The in vitro and in vivo drug release studies described a sustained release pattern of febuxostat and increased relative bioavailability by 286.63 %. Considering these findings, this chitosan nanoparticle DDS can further be used for improving the EE and bioavailability of hydrophobic drugs.

Pluronic F-68 and F-127 Based Nanomedicines for Advancing Combination Cancer Therapy.

Pluronics are amphiphilic triblock copolymers composed of two hydrophilic poly (ethylene oxide) (PEO) chains linked via a central hydrophobic polypropylene oxide (PPO). Owing to their low molecular weight polymer and greater number of PEO segments, Pluronics induce micelle formation and gelation at critical micelle concentrations and temperatures. Pluronics F-68 and F-127 are the only United States (U.S.) FDA-approved classes of Pluronics and have been extensively used as materials for living bodies. Owing to the fascinating characteristics of Pluronics, many studies have suggested their role in biomedical applications, such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. As a result, various studies have been performed using Pluronics as a tool in nanomedicine and targeted delivery systems. This review sought to describe the delivery of therapeutic cargos using Pluronic F-68 and F-127-based cancer nanomedicines and their composites for combination therapy.

Facile Fabrication of α-Bisabolol Nanoparticles with Improved Antioxidant and Antibacterial Effects.

Bioactive compounds are widely used in the bio-industry because of their antioxidant and antibacterial activities. Because of excessive oxidative stress, which causes various diseases in humans, and because preservatives used in bioproducts cause allergies and contact dermatitis, it is important to use natural bioactive compounds in bioproducts to minimize oxidative stress. α-bisabolol (ABS) is a natural compound with both antioxidant and antibacterial properties. However, its water-insolubility makes its utilization in bioproducts difficult. In this study, ABS-loaded polyglyceryl-4 caprate nanoparticles (ABS@NPs) with improved aqueous stability and ABS loading were fabricated using an encapsulation method. The long-term stability of the ABS@NPs was analyzed with dynamic light scattering and methylene blue-staining to determine the optimized ABS concentration in ABS@NPs (10 wt%). The ABS@NPs exhibited excellent antioxidant activity, according to the 2,2-diphenyl-1-picrylhydrazyl assay and in vitro reactive oxygen species generation in NIH-3T3 fibroblast cells, and an outstanding antibacterial effect, as determined using the Staphylococcus aureus colony-counting method. Furthermore, we evaluated the biocompatibility of the ABS@NPs in vitro. This study suggests that ABS@NPs with improved antioxidant and antibacterial properties can be used to treat diseases related to various oxidative stresses and can be applied in many fields, such as pharmaceuticals, cosmetics, and foods.

Mesoporous Silica Nanoparticles as a Gene Delivery Platform for Cancer Therapy.

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.

Development of poly(lactide-co-glycolide) microparticles for sustained delivery of meloxicam.

Poly(lactide-co-glycolide) (PLGA) polymers have been widely used for drug delivery due to their biodegradability and biocompatibility. One of the objectives of encapsulating a drug in PLGA microparticles (MPs) is to achieve an extended supply of the drug through sustained release, which can range from weeks to months. Focusing on the applications needing a relatively short-term delivery, we investigated formulation strategies to achieve a drug release from PLGA MPs for two weeks, using meloxicam as a model compound. PLGA MPs produced by the traditional oil/water (O/W) single emulsion method showed only an initial burst release with minimal increase in later-phase drug release. Alternatively, encapsulating meloxicam as solid helped reduce the initial burst release. The inclusion of magnesium hydroxide [Mg(OH)2] enhanced later-phase drug release by neutralizing the developing acidity that limited the drug dissolution. The variation of solid meloxicam and Mg(OH)2 quantities allowed for flexible control of meloxicam release, yielding MPs with distinct in vitro release kinetics. When subcutaneously injected into rats, the MPs with relatively slow in vitro drug release kinetics showed in vivo drug absorption profiles consistent with in vitro trend. However, the MPs that rapidly released meloxicam showed an attenuated in vivo absorption, suggesting premature precipitation of fast-released meloxicam. In summary, this study demonstrated the feasibility of controlling drug release from the PLGA MPs over weeks based on the physical state of the encapsulated drug and the inclusion of Mg(OH)2 to neutralize the microenvironmental pH of the MPs.

Engineering microenvironment of biodegradable polyester systems for drug stability and release control.

Polymeric systems made of poly(lactic acid) or poly(lactic-co-glycolic acid) are widely used for long-term delivery of small and large molecules. The advantages of poly(lactic acid)/poly(lactic-co-glycolic acid) systems include biodegradability, safety and a long history of use in US FDA-approved products. However, as drugs delivered by the polymeric systems and their applications become more diverse, the significance of microenvironment change of degrading systems on long-term drug stability and release kinetics has gained renewed attention. In this review, we discuss various issues experienced with acidifying microenvironment of biodegradable polymer systems and approaches to overcome the detrimental effects of polymer degradation on drug stability and release control.

Developing Protein-Based Nanoparticles as Versatile Delivery Systems for Cancer Therapy and Imaging.

In recent years, it has become apparent that cancer nanomedicine's reliance on synthetic nanoparticles as drug delivery systems has resulted in limited clinical outcomes. This is mostly due to a poor understanding of their "bio-nano" interactions. Protein-based nanoparticles (PNPs) are rapidly emerging as versatile vehicles for the delivery of therapeutic and diagnostic agents, offering a potential alternative to synthetic nanoparticles. PNPs are abundant in nature, genetically and chemically modifiable, monodisperse, biocompatible, and biodegradable. To harness their full clinical potential, it is important for PNPs to be accurately designed and engineered. In this review, we outline the recent advancements and applications of PNPs in cancer nanomedicine. We also discuss the future directions for PNP research and what challenges must be overcome to ensure their translation into the clinic.

Pluronics: Intelligent building units for targeted cancer therapy and molecular imaging.

Pluronics are triblock copolymers, in which two hydrophilic poly (ethylene oxide) (PEO) blocks are connected via a hydrophobic poly propylene oxide (PPO) block. Because of their low molecular weight and high content of PEO, Pluronics have demonstrated the micellization phenomenon, which is dependent on temperature and/or concentration. With an understanding of micellization phenomenon in more detail, information on the morphology, micelle core radius, aggregation behavior with critical micelle concentration (CMC) and critical micelle temperature (CMT) and so on has been revealed. Based on this acquired information, various studies have been performed for biomedical applications such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. This review discusses the delivery of small molecules and macromolecules using Pluronic-based NPs and their composites.

Assembly of polymer micelles through the sol-gel transition for effective cancer therapy.

Photo-induced apoptosis-targeted chemotherapy (PIATC) was designed and characterized to propose a new protocol for improved chemotherapy. Intratumoral injection was selected as the mode of administration of the anticancer drug, doxorubicin (DOX). To extend the retention time of DOX at the tumor parenchyma, in-situ gel formation was induced through the sol-gel transition of the Pluronic NPs containing a prodrug of DOX or a photosensitizer. The prodrug (DEVD-S-DOX) was designed to be inactive with a peptide moiety (Aspartic acid-Glutamic acid-Valine-Aspartic acid: DEVD) linked to DOX and to be cleaved into free DOX by caspase-3 expressed with apoptosis. For reactive oxygen species (ROS)-mediated apoptosis, photo-irradiation with methylene blue (MB, photosensitizer) was utilized. The sol-gel transition of the Pluronic NPs containing reactive species, DEVD-S-DOX or MB, was examined by measuring the cloud point and the gel strength in response to temperature change. ROS-mediated apoptosis was observed by measuring the ROS and membrane integrity with induced apoptosis. The in vivo antitumor efficacy of PIATC was measured with a cardiotoxicity assay in tumor-bearing mice.

Doxorubicin/heparin composite nanoparticles for caspase-activated prodrug chemotherapy.

Caspase-activated prodrug chemotherapy is introduced and demonstrated using the composite nanoparticles (NPs), which deliver doxorubicin (DOX) and DEVD-S-DOX together to the tumor tissue. DEVD-S-DOX, DOX linked to a peptide moiety (DEVD), is a prodrug that is cleaved into free DOX by caspase-3 upon apoptosis. DEVD-S-DOX has no therapeutic efficacy, but it changes into free DOX with the expression of caspase-3. With the accumulation of the composite NPs in the tumor tissue by the enhanced permeation and retention (EPR) effect, a small exposure of DOX in the tumor cells initiated apoptosis in a localized area of the tumor tissue, which induced caspase-3 activation. Cleavage of DEVD-S-DOX into free DOX by caspase-3 continued with repetitive activation of caspase-3 and cleavage of DEVD-S-DOX at the tumor site. The composite NPs were characterized with transmittance electron microscopy (TEM) and particle size analyzer. We then evaluated the nanoparticle drug release, therapeutic efficacy, and in vivo biodistribution for tumor targeting using a non-invasive live animal imaging technology and the quantification of DOX with high performance liquid chromatography. DOX-induced apoptosis-targeted chemotherapy (DIATC) was verified by in vitro/in vivo DEVD-S-DOX response to free DOX and cellular uptake behavior of the composite NPs with flow cytometry analysis. Significant antitumor efficacy with minimal cardiotoxicity was also observed, which supported DIATC for improved chemotherapy.

The multilayer nanoparticles for deep penetration of docetaxel into tumor parenchyma to overcome tumor microenvironment.

Deep penetration of the anticancer drug, docetaxel (DTX), into tumor parenchyma was demonstrated to achieve improved chemotherapy. For this purpose, a multistage nanostructure was designed and characterized using the multilayer nanoparticles (NPs). The multilayer NPs had a core/shell structure. The core was composed of the DTX-loaded Pluronic NPs (diameter: 12nm) that were transferred into the inner side of vesicles to form the vesicle NPs. Förster resonance energy transfer (FRET) in the NPs was observed to verify the incorporation of the DTX-loaded Pluronic NPs into the inner side of the vesicles during the formation of the vesicle NPs. Subsequently, the vesicle NPs were stabilized through Pluronic-lipid bilayer interaction to form the multilayer NPs. To examine the morphology and size distribution of the multilayer NPs, transmittance electron microscopy and dynamic light scattering were used. In vitro release behavior and toxicity were observed to verify the functionality of the multilayer NPs as nanocarriers for cancer therapy. Multistage functionality was evaluated by cellular uptake and tissue distribution behaviors of the multilayer NPs. The biodistribution of the multilayer NPs and their antitumor efficacy were also observed to understand the role of multistage functionality for improved chemotherapy.