Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology

Modulation of immune response by nanoparticle-based immunotherapy against food allergens

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy

Time Trends and Regional Variation in Prevalence of Asthma and Associated Factors in Saudi Arabia: A Systematic Review and Meta-Analysis

Background. Asthma is the most common reason for emergency visits to hospital and loss of productive hours. In Saudi Arabia, asthma affects more than 2 million people and majority of them have uncontrolled asthma with their quality of life adversely being impacted. It is well known that the prevalence of asthma has been increasing in many places around the world in the last few decades. The present review attempted to identify studies on asthma and associated factors in Saudi Arabian population and assess their time trends and regional variation. Methods. The titles and abstracts of retrieved articles were compared to delete duplication and irrelevant data. A data collection form was designed to extract several key components from selected articles like bibliographic information on the article, study population, and sample size. Extracted information was grouped appropriately for data analysis. Database search retrieved 71 articles. Applying inclusion and exclusion criteria, 40 articles were excluded and 31 qualified full articles were included for the review. Results. Among 31 retained studies, Riyadh had the highest publication output followed by Jeddah. Ten studies were based on ISAAC and 5 on non-ISAAC questionnaires while 5 studies were genetic studies conducted to unravel the genetic basis of asthma. Most of the studies were conducted on pediatric subjects of less than 16 years of age. Sample sizes ranged from less than 150 to more than 10000 with study settings being predominantly urban (22 studies). The pooled weighted prevalence rates of asthma, lifetime wheeze, and rhinitis were 14.3% (95% CI: 13.4–15.2), 16.5 (95% CI 15.5–17.4), and 21.4 (95% CI 20.5–22.3), respectively. An increase in asthma prevalence from 1990 to 2000 along with a stabilized or not so significant decline in the prevalence from 2010 to 2016 was observed. Conclusion. The prevalence of asthma varied in different regions without any disparity in prevalence in the rural and urban areas of Saudi Arabia. The understanding of genetic variability and recognition of risk factors in asthma patients can greatly help in individualizing the therapy for the management and control of asthma

Preparation and characterization of a curcumin nanoemulsion gel for the effective treatment of mycoses

Abstract Fungal infections of skin including mycoses are one of the most common infections in skin or skins. Mycosis is caused by dermatophytes, non-dermatophyte moulds and yeasts. Various studies show different drugs to treat mycoses, yet there is need to treat it with applied drugs delivery. This study was designed to prepare a bio curcumin (CMN) nanoemulsion (CMN-NEs) for transdermal administration to treat mycoses. The self-nanoemulsification approach was used to prepare a nanoemulsion (NE), utilizing an oil phase consisting of Cremophor EL 100 (Cre EL), glyceryl monooleate (GMO), and polyethylene glycol 5000 (PEG 5000). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), Fourier transform infrared (FTIR) spectrophotometric analysis, and morphological analyses were performed to evaluate the nanoemulsion (NE). The in vitro permeation of CMN was investigated using a modified vertical diffusion cell with an activated dialysis membrane bag. Among all the formulations, a stable, spontaneously produced nanoemulsion was determined with 250 mg of CMN loaded with 10 g of the oil phase. The average droplet size, ZP, and PDI of CMN-NEs were 90.0 ± 2.1 nm, − 7.4 ± 0.4, and 0.171 ± 0.03 mV, respectively. The release kinetics of CMN differed from zero order with a Higuchi release profile as a result of nanoemulsification, which also significantly increased the flux of CMN permeating from the hydrophilic matrix gel. Overall, the prepared nanoemulsion system not only increased the permeability of CMN but also protected it against chemical deterioration. Both CMN-ME (24.0 ± 0.31 mm) and CMN-NE gel (29.6 ± 0.25 mm) had zones of inhibition against Candida albicans that were significantly larger than those of marketed Itrostred gel (21.5 ± 0.34 mm). The prepared CMN-NE improved the bioavailability, better skin penetration, and the CMN-NE gel enhanced the release of CMN from the gel matrix on mycotic patients

Quality by design aided self-nano emulsifying drug delivery systems development for the oral delivery of Benidipine: Improvement of biopharmaceutical performance

The primary objective of the research effort is to establish efficient solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for benidipine (BD) through the systematic application of a quality-by-design (QbD)-based paradigm. Utilizing Labrafil M 2125 CS, Kolliphor EL, and Transcutol P, the BD-S-SNEDDS were created. The central composite design was adopted to optimize numerous components. Zeta potential, drug concentration, resistance to dilution, pH, refractive index, viscosity, thermodynamic stability, and cloud point were further investigated in the most efficient formulation, BD14, which had a globule size of 156.20 ± 2.40 nm, PDI of 0.25, zeta potential of −17.36 ± 0.18 mV, self-emulsification time of 65.21 ± 1.95 s, % transmittance of 99.80 ± 0.70%, and drug release of 92.65 ± 1.70% at 15 min. S-SNEDDS were formulated using the adsorption process and investigated via Fourier transform infrared spectroscopy, Differential scanning calorimeter, Scanning electron microscopy, and powder X-ray diffraction. Optimized S-SNEDDS batch BD14 dramatically decreased blood pressure in rats in contrast to the pure drug and the commercial product, according to a pharmacodynamics investigation. Accelerated stability tests validated the product’s stability. Therefore, the development of oral S-SNEDDS of BD may be advantageous for raising BD's water solubility and expanding their releasing capabilities, thereby boosting oral absorption.</p

Simvastatin-Encapsulated Topical Liposomal Gel for Augmented Wound Healing: Optimization Using the Box-Behnken Model, Evaluations, and In Vivo Studies

Statins function beyond regulating cholesterol and, when administered systemically, can promote wound healing. However, studies have yet to explore the topical use of statins for wound healing. The present study demonstrated the topical administration of SIM and aimed to formulate, evaluate, and optimize Simvastatin (SIM)-encapsulated liposome gel carrier systems to facilitate successful topical wound healing. Liposomes containing SIM were formulated and optimized via a response surface methodology (RSM) using the thin-film hydration method. The effects of formulation variables, including the 1,2-dioleoyloxy-3-trimethylammoniumpropan (DOTAP) concentration, Span 80 concentration, and cholesterol concentration, on zeta potential (mV), entrapment efficacy (%), and particle size (nm) were studied. The optimized liposome formulation (F-07) exhibited a zeta potential value of 16.56 ± 2.51 mV, revealing robust stability and a high SIM encapsulation efficiency of 95.6 ± 4.2%, whereas its particle size of 190.3 ± 3.3 nm confirmed its stability and structural integrity. The optimized liposome gel demonstrated pseudoplastic flow behavior. This property is advantageous in topical drug delivery systems because of its ease of application, improved spreadability, and enhanced penetration, demonstrating prolonged SIM release. The assessment of the wound healing efficacy of the optimized liposomal gel formulation demonstrated a substantial decrease in wound size in mice on the sixteenth day post-wounding. These findings suggest that the use of liposomal gels is a potential drug delivery strategy for incorporating SIM, thereby augmenting its effectiveness in promoting wound healing

Box-Behnken Design-Based Optimization and Evaluation of Lipid-Based Nano Drug Delivery System for Brain Targeting of Bromocriptine

Bromocriptine (BCR) presents poor bioavailability when administered orally because of its low solubility and prolonged first-pass metabolism. This poses a significant challenge in its utilization as an effective treatment for managing Parkinson’s disease (PD). The utilization of lipid nanoparticles can be a promising approach to overcome the limitations of BCR bioavailability. The aim of the research work was to develop and evaluate bromocriptine-loaded solid lipid nanoparticles (BCR-SLN) and bromocriptine-loaded nanostructured lipid carriers (BCR-NLC) employing the Box-Behnken design (BBD). BCR-SLNs and BCR-NLCs were developed using the high-pressure homogenization method. The prepared nanoparticles were characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE). In vitro drug release, cytotoxicity studies, in vivo plasma pharmacokinetic, and brain distribution studies evaluated the optimized lipid nanoparticles. The optimized BCR-SLN had a PS of 219.21 ± 1.3 nm, PDI of 0.22 ± 0.02, and EE of 72.2 ± 0.5. The PS, PDI, and EE of optimized BCR-NLC formulation were found to be 182.87 ± 2.2, 0.16 ± 0.004, and 83.57 ± 1.8, respectively. The in vitro release profile of BCR-SLN and BCR-NLC showed a biphasic pattern, immediate release, and then trailed due to the sustained release. Furthermore, a pharmacokinetic study indicated that both the optimized BCR-SLN and BCR-NLC formulations improve the plasma and brain bioavailability of the drug compared to the BCR solution. Based on the research findings, it can be concluded that the BCR-loaded lipid nanoparticles could be a promising carrier by enhancing the BBB penetration of the drug and helping in the improvement of the bioavailability and therapeutic efficacy of BCR in the management of PD