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Messenger RNA (mRNA) vaccine development for preventive and therapeutic applications has evolved rapidly over the last decade. The mRVNA vaccine has proven therapeutic efficacy in various applications, including infectious disease, immunotherapy, genetic disorders, regenerative medicine, and cancer. Many mRNA vaccines have made it to clinical trials, and a couple have obtained FDA approval. This emerging therapeutic approach has several advantages over conventional methods: safety; efficacy; adaptability; bulk production; and cost-effectiveness. However, it is worth mentioning that the delivery to the target site and in vivo degradation and thermal stability are boundaries that can alter their efficacy and outcomes. In this review, we shed light on different types of mRNA vaccines, their mode of action, and the process to optimize their development and overcome their limitations. We also have explored various delivery systems focusing on the nanoparticle-mediated delivery of the mRNA vaccine. Generally, the delivery system plays a vital role in enhancing mRNA vaccine stability, biocompatibility, and homing to the desired cells and tissues. In addition to their function as a delivery vehicle, they serve as a compartment that shields and protects the mRNA molecules against physical, chemical, and biological activities that can alter their efficiency. Finally, we focused on the future considerations that should be attained for safer and more efficient mRNA application underlining the advantages and disadvantages of the current mRNA vaccines.

Neurodegenerative and neuronal-related diseases are major public health concerns. Human vulnerability to neurodegenerative diseases (NDDs) increases with age. Neuronal hormones and neurotransmitters are major determinant factors regulating brain structure and functions. The implications of environmental and climatic changes emerged recently as influence factors on numerous diseases. However, the complex interaction of neurotransmitters and neuronal hormones and their depletion under environmental and climatic influences on NDDs are not well established in the literature. In this review, we aim to explore the connection between the environmental and climatic factors to NDDs and to highlight the available and potential therapeutic interventions that could use to improve the quality of life and reduce susceptibility to NDDs.

Aedes aegypti mosquitoes carrying self-spreading, virus-blocking Wolbachia bacteria are being deployed to suppress dengue transmission. However, there are challenges in applying this technology in extreme environments. We introduced two Wolbachia strains into Ae . aegypti from Saudi Arabia for a release program in the hot coastal city of Jeddah. Wolbachia reduced infection and dissemination of dengue virus (DENV2) in Saudi Arabian mosquitoes and showed complete maternal transmission and cytoplasmic incompatibility. Wolbachia reduced egg hatch under a range of environmental conditions, with the Wolbachia strains showing differential thermal stability. Wolbachia effects were similar across mosquito genetic backgrounds but we found evidence of local adaptation, with Saudi Arabian mosquitoes having lower egg viability but higher adult desiccation tolerance than Australian mosquitoes. Genetic background effects will influence Wolbachia invasion dynamics, reinforcing the need to use local genotypes for mosquito release programs, particularly in extreme environments like Jeddah. Our comprehensive characterization of Wolbachia strains provides a foundation for Wolbachia -based disease interventions in harsh climates.

Chronic obstructive pulmonary disease (COPD) is a progressive lung dysfunction caused mainly by inhaling toxic particles and cigarette smoking (CS). The continuous exposure to ruinous molecules can lead to abnormal inflammatory responses, permanent damages to the respiratory system, and irreversible pathological changes. Other factors, such as genetics and aging, influence the development of COPD. In the last decade, accumulating evidence suggested that mitochondrial alteration, including mitochondrial DNA damage, increased mitochondrial reactive oxygen species (ROS), abnormal autophagy, and apoptosis, have been implicated in the pathogenesis of COPD. The alteration can also extend to epigenetics, namely DNA methylation, histone modification, and non-coding RNA. This review will discuss the recent progressions in COPD pathology, pathophysiology, and molecular pathways. More focus will be shed on mitochondrial and epigenetic variations related to COPD development and the role of nanomedicine as a potential tool for the prevention and treatment of this disease.

The increasing prevalence of antimicrobial-resistant (AMR) bacteria along with the limited development of antimicrobials warrant investigating novel antimicrobial modalities. Emerging inorganic engineered nanomaterials (ENMs), most notably silver nanoparticles (AgNPs), have demonstrated superior antimicrobial properties. However, AgNPs, particularly those of small size, could exert overt toxicity to mammalian cells. This study investigated whether combining AgNPs and conventional antimicrobials would produce a synergistic response and determined the optimal and safe minimum inhibitory concentration (MIC) range against several wild-type Gram-positive and -negative strains and three different clinical isolates of AMR Klebsiella pneumoniae. Furthermore, the cytotoxicity of the synergistic combinations was assessed in a human hepatocyte model. The results showed that the AgNPs (15–25 nm) were effective against Gram-negative bacteria (MIC of 16–128 µg/mL) but not Gram-positive strains (MIC of 256 µg/mL). Both wild-type and AMR K. pneumoniae had similar MIC values following exposure to AgNPs. Importantly, co-exposure to combinations of AgNPs and antimicrobial agents, including kanamycin, colistin, rifampicin, and vancomycin, displayed synergy against both wild-type and AMR K. pneumoniae isolates (except for vancomycin against AMR strain I). Notably, the tested combinations demonstrated no to minimal toxicity against hepatocytes. Altogether, this study indicates the potential of combining AgNPs with conventional antimicrobials to overcome AMR bacteria.

The inadequate eradication of pulmonary infections and chronic inflammation are significant complications in cystic fibrosis (CF) patients, who usually suffer from persistent and frequent lung infections caused by several pathogens, particularly Pseudomonas aeruginosa (P. aeruginosa). The ability of pathogenic microbes to protect themselves from biofilms leads to the development of an innate immune response and antibiotic resistance. In the present work, a reference bacterial strain of P. aeruginosa (PA01) and a multidrug-resistant isolate (MDR 7067) were used to explore the microbial susceptibility to three antibiotics (ceftazidime, imipenem, and tobramycin) and an anti-biofilm peptide (IDR-1018 peptide) using the minimum inhibition concentration (MIC). The most effective antibiotic was then encapsulated into liposomal nanoparticles and the IDR-1018 peptide with antibacterial activity, and the ability to disrupt the produced biofilm against PA01 and MDR 7067 was assessed. The MIC evaluation of the tobramycin antibacterial activity showed an insignificant effect on the liposomes loaded with tobramycin and liposomes encapsulating tobramycin and IDR-1018 against both P. aeruginosa strains to free tobramycin. Nevertheless, the biofilm formation was significantly reduced (p < 0.05) at concentrations of ≥4 μg/mL and ≤32 μg/mL for PA01 and ≤32 μg/mL for MDR 7067 when loading tobramycin into liposomes, with or without the anti-biofilm peptide compared to the free antibiotic, empty liposomes, and IDR-1018-loaded liposomes. A tobramycin concentration of ≤256 µg/mL was safe when exposed to a lung carcinoma cell line upon its encapsulation into the liposomal formulation. Tobramycin-loaded liposomes could be a potential candidate for treating lung-infected animal models owing to the high therapeutic efficacy and safety profile of this system compared to the free administration of the antibiotic.

Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies’ major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine.

Major depressive disorder (MMD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD fail to achieve response or remission leading to treatment-resistant depression (TRD). One of the psychopharmacological strategies to overcome TRD is using a combination of an antipsychotic as an augmenting agent with selective serotonin reuptake inhibitors (SSRIs). Among which, an atypical antipsychotic, quetiapine (QUE), and an SSRI, escitalopram (ESC), were formulated as a fixed-dose combination as a fast-dissolving film by coaxial electrospinning. The resultant fiber’s morphology was studied. SEM images showed that the drug-loaded fibers were smooth, un-beaded, and non-porous with a fiber diameter of 0.9 ± 0.1 µm, while the TEM images illustrated the distinctive layers of the core and shell, confirming the successful preparation of these fibers. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies confirmed that both drugs were amorphously distributed within the drug-loaded fibers. The drug-loaded fibers exhibited a disintegration time of 2 s, which accelerated the release of both drugs (50% after 5 min) making it an attractive formulation for oral mucosal delivery. The ex vivo permeability study demonstrated that QUE was permeated through the buccal membrane, but not ESC that might be hindered by the buccal epithelium and the intercellular lipids. Overall, the developed coaxial fibers could be a potential buccal dosage form that could be attributed to higher acceptability and adherence among vulnerable patients, particularly mentally ill patients.

Geriatric patients are more likely to suffer from multiple chronic diseases that require using several drugs, which are commonly ingested. However, to enhance geriatric patients’ convenience, the electrospun nanofiber system was previously proven to be a successful alternative for the existing oral dosage forms, i.e., tablets and capsules. These nanofibers prepared either as single- or multi-layered fibers could hold at least one active compound in each layer. They might also be fabricated as ultra-disintegrated fibrous films for oral cavity administration, i.e., buccal or sublingual, to improve the bioavailability and intake of the administered drugs. Therefore, in this work, a combination of nifedipine and atorvastatin calcium, which are frequently prescribed for hypertension and hyperlipidemia patients, respectively, was prepared in a coaxial electrospinning system for buccal administration. Scanning electron microscopy image showed the successful preparation of smooth, non-beaded, and non-porous surfaces of the drug-loaded nanofibers with an average fiber diameter of 968 ± 198 nm. In contrast, transmission electron microscopy distinguished the inner and outer layers of those nanofibers. The disintegration of the drug-loaded nanofibers was ≤12 s, allowing the rapid release of nifedipine and atorvastatin calcium to 61% and 47%, respectively, after 10 min, while a complete drug release was achieved after 120 min. In vitro, a drug permeation study using Franz diffusion showed that the permeation of both drugs from the core–shell nanofibers was enhanced significantly (p < 0.05) compared to the drugs in a solution form. In conclusion, the development of drug-loaded nanofibers containing nifedipine and atorvastatin calcium can be a potential buccal delivery system.

[Display omitted] Hand hygiene is one of the effective measures for reducing the transmission of infections. Alcohol-based hand sanitizers containing ethanol or isopropanol are considered efficient alternatives to handwashing with water and soap. Despite being effective against a broad-spectrum of microbes, fining an effective alternative to the alcohol-based hand sanitizers became a necessity owning to the limitations associated with their use, such as skin dryness, irritant contact dermatitis, and intoxication upon their accidental ingestion. Furthermore, in certain circumstances when the demand for alcohol exceeds the supply, like in the current COVID19 pandemic, formulating an effective non-alcoholic hand sanitizer would be a potential solution. Therefore, in this study, a non-alcoholic hand sanitizer containing benzalkonium chloride (BKC) as an active ingredient was prepared and evaluated as a less irritant and more persistent hand sanitizer gel. The hand gel was characterized by pH, viscosity, and spreadability. Results showed that this product has low viscosity, high spreadability and pH of 6.3, which is less likely to cause skin irritation. The antibacterial assessment (zone of inhibition) of the BKC-based hand sanitizer demonstrated antibacterial activities against nine out of eleven gram-positive and gram-negative bacterial strains, while the acceptability study on ten participants showed no signs of skin irritation nor redness upon its application. Consequently, this non-alcoholic based hand sanitizer is suggested as a potential alternative to alcohol-based hand gels.