Abstract Background Wound healing is a natural but complex process that can be delayed by infection. Rosuvastatin calcium (RVS) is an anti-hyperlipidemic that was recently reported to have a wound healing capability. The study aimed to investigate the impact of combining RVS with Levofloxacin (LV) on wound healing. A physically crosslinked polyvinyl alcohol (PVA) film loaded with RVS and LV was formulated as wound dressing. Formulation optimization was carried out using Box–Behnken design. The effect of independent variables (PVA and propylene glycol concentrations and the number of freeze–thaw cycles) on tensile strength (TS), elongation to break (%EB) and in vitro drugs’ release was studied. For simultaneous RVS and LV quantification in the formulations and pure form, three spectrophotometric methods: derivative of ratio spectrophotometry, first derivative and mean centering, were developed. Also, their greenness was evaluated by the Analytical Eco-Scale and the Green Analytical Procedure Index. Then, the wound healing effect of the optimized wound dressing was evaluated in rat models. Results The optimized dressing had sufficient mechanical strength (9.45 ± 0.67 MPa), adequate flexibility (112.6 ± 3.8% EB) and suitable drug release (52.3 ± 1.4% for LV and 38.99 ± 1.6% for RVS after 12 h). The proposed methods were validated following ICH guidelines, and greenness assessment suggested their very low environmental effect. The wound healing evaluation showed a higher wound contraction percentage when RVS was combined to LV. A histopathological study confirmed marked improvement in animals treated with combined formula with lowest inflammatory infiltration and optimum epithelialization, compared to other groups. Conclusion Study findings suggest that combined LV-RVS dressing would be a beneficial platform with potentiated wound healing capacity. Graphic abstract

Peptide nucleic acid (PNA) is a neutral analogue of DNA/RNA used for diverse antisense and antigene applications. PNA exhibits excellent binding affinity, sequence specificity, resistance to enzymatic degradation, and minimal electrostatic interactions with target oligonucleotides. PNA's potential in therapeutic applications is not fully explored compared to other antisense oligonucleotides (ASOs). PNA designs have been used to target a wide array of microRNAs (miRs) for the potential treatment of various cancers. miRNAs are short, non-coding RNA molecules that regulate post-translational gene expression. In cancer, upregulated miRNA expression plays a crucial role in tumor initiation and progression. The inefficient cellular uptake of PNAs limits their clinical translation. The limitations of PNA prompted the engineering of two classes of nanoparticles (NPs): polymeric-based and silica-based NPs to facilitate the intracellular delivery of PNA in targeted tumor cells and enhance their therapeutic potential in cancer therapy. In this review, we searched the PubMed, Web of Science, and Google Scholar databases, with no publication date restriction, to explore various applications of PNA-loaded nanoparticles in cancer therapy. We have discussed various PNA-loaded nanoparticles used across a range of cancer cell lines and mouse models for cancer therapy.

Background: Norfloxacin (NFX) is a wide-spectrum antibacterial agent that suffers from low water solubility and first-pass metabolism. This diminishes its oral bioavailability by 60-70%. Objective: This work aims to formulate a topical gel of NFX-loaded lipid polymer hybrid nanoparticles (NFX-LPHNPs) that combine the merits of liposomes and polymeric nanoparticles to overcome these problems. Methods: NFX-LPHNPs formulations were developed using Precirol ATO (lipid) and Eudragit RL100 (polymer). They were characterized for particle size, uniformity of distribution, entrapment efficiency, zeta potential, and in-vitro release. Box–Behnken design was applied to study sequentially different variables' impact on material attributes. Then the optimized formula was re-evaluated, and incorporated in an HPMC-gel formulation. The gel formulation was evaluated for its physical properties, in vitro-release, and antibacterial activity. Results: NFX-LPHNPs exhibited particle sizes ranging from 28.92 to 730.30 nm. Particles were uniformly distributed with a positively charged surface (indicated by zeta potential with values from +3.91 to +60.2 mV). Formulations showed a % cumulative drug release of 87.9-100% in 8 h. The optimized formula showed a satisfied fit of measured-to-predicted responses with 159 nm particle size, 92.61% release and 79.2% entrapment efficiency. Gel formulation showed a sustained release over 24h. Antibacterial testing against Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa revealed enhanced activity of NFX-LPHNPs against these pathogens compared to bare NFX loaded gel. Conclusion: These results illustrated the high potential of lipid-polymer hybrid nanoparticles to improve NFX activity against resistant pathogens common in burn infections. Moreover, the topical application helps overcome Norfloxacin oral-associated problems.

Etoricoxib (Et) is selective COX-2 inhibitor with several drawbacks after oral administration. Current study focused on formulating targeted Et cubogel for osteoarthritis management. Interaction between formulation factors; (glyceryl-monooleate (GMO) and Poloxamer407 (Px)) concentrations and process parameters (melting/solvent-evaporation preparation methods) was investigated using D-optimal design. Considered levels were 3, 5 and 7% for GMO and 0.5,0.75 and 1% for Px. Effect of selected variables on particle size (PS) and entrapment efficiency (EE) of Et cubosomes was studied using Design Expert software. Optimized formulation was studied for zeta potential, TEM, and Et release. Optimum formula was loaded into gel formulations and subjected to physical characterization and in-vitro Et release. Selected cubogel was evaluated for ex-vivo permeation, and anti-inflammatory activity using carrageenan-induced edema model. Optimum formulation (6.5% GMO,1% Px , melting preparation method) had PS of 58.6 ± 0.51 nm, EE of 96.1 ± 1.5%, zeta potential of -26.6 ± 0.66 mV and cubic structure as indicated by TEM. Formulated cubogels had acceptable physical properties with sustained release depending on gelling agent type and concentration. Ex-vivo permeation confirmed higher permeability for Et cubogel than Etgel. Anti-inflammatory study confirmed enhanced (p < 0.05) anti-inflammatory activity of Et cubogel as compared to Et gel. Hence, the present study presents Et cubgel formulation as anti-inflammatory remedy.

Etoricoxib (Et), a new potent COX-2 anti-inflammatory drug that suffers from severe side effects after oral administration. The present study is concerned with preparation and characterization of transdermal gel formulations containing Et cubosomes nanoparticles. Et cubosome dispersions were formulated using different concentrations of lipid phase Glycerol Monooleate (GMO), nonionic surfactant Poloxamer 407 (P407) and water as aqueous phase. The prepared Et cubosomal dispersions were characterized for % drug content, % entrapment efficiency (EE), particle size, and in vitro drug release. Formulation with highest EE (92.0 ± 1.6 %), small particle size (63.5 ± 1.8 nm) and acceptable drug release profile (S9) was further evaluated for zeta potential and investigated for its internal structure using the transmission electron microscope (TEM). Results confirmed formation of cubic to spherical shaped particles with acceptable zeta potential (-20 ± 0.379 mV). Selected formulation was incorporated in different gel formulations using CMC-Na (1, 1.5 % w/w) as gelling agent and glycerol (2.5, 5, 7.5 % w/w) as penetration enhancer. The cubosomal gels were characterized along with drug loaded gel for macroscopic, physical properties and in vitro drug release. Results confirmed acceptable macroscopic, physical properties with variable drug release profiles depending on gelling agent concentration as well as glycerol concentrations. Selected gel formulation with favorable drug release profile (G3) was further evaluated for ex vivo permeation. Results showed enhanced permeation for G3 compared to Et gel. The developed Et-loaded cubosomal gel offers a promising transdermal method for treating arthritis that will be applied directly to the skin.

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics.

Background Alzheimer's disease (AD) is a neurological disease that causes memory loss over time. Current therapies are limited and frequently inadequate. Epigallocatechin gallate (EGCG), has antioxidant, anti-inflammatory, antifibrosis, anti-remodeling and tissue-protective qualities that may be effective in treatment of different diseases, including AD. Because of nanoparticles' high surface area, they can enhance solubility, stability, pharmacokinetics and biodistribution, and diminish toxicities. Besides, lipid nanoparticles have a high binding affinity that can enhance the rate of drug transport across BBB. So, EGCG nanoparticles represent a promising treatment for AD.Objectives This systematic review sought to assess the efficacy of EGCG nanoparticles against AD in rat/mouse models.Methods Study was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO. Electronic databases were searched to discover relevant studies published up to October 2022.Results Two studies met the inclusion criteria out of 1338 and were included in this systematic review. Collectively, the results indicate that EGCG has a significant potential for reducing AD pathology and improving cognitive deficits in rat/mouse models. The formulated particles were in the nanometer range, as indicated by TEM, with good particle size control and stability. EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG. Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats.Conclusion This systematic analysis of the two studies included showed that EGCG nanoparticles are efficacious as a potential therapeutic intervention for AD in rat/mouse models. However, limited number of studies found indicates insufficient data in this research point that requires further investigation by experimental studies.

Establish measures that predict academic progression and need for metacognitive remediation in Pharm.D. students enrolled in calculations courses at the University of Saint Joseph. Hypotheses to be tested: 1) students with strong math skills would constantly outperform less numerate students, 2) completion of calculations courses would close the performance gap across the class.

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.

Background: Augmented reality (AR) is a technological approach which combines virtual objects such as text, pictures or videos with physical objects (real-world). The study aimed to design, implement and validate a mobile-based AR application, as a self-paced, interactive, student-centered learning tool be used in the pharmaceutical compounding laboratory course for first year pharmacy students. Method: A mobile-based AR application (Amplified Rx app; HeyPayLess Inc) compatible with iOS and android operating system was developed. A cross-over study design was conducted where alternatively, one group was subjected to ARx app implementation in 8 formulations and the other group served as control. The reception and benefits to students were assessed via a 10 questions survey. In this case, 69 (2019) and 55 (2020) students participated in the study. Result: Students’ use of ARx app was increased in 2020 which indicates its usefulness. For acceptability, leaners enjoyed interactive materials and tutorial videos were the most used and appealing item. Learners described the installation, scanning and operation to be very easy in both years. 86.95% of learners were confident conducting the experiments with the assistance of ARx app in 2019 and increased to 92.73% in 2020. 33.33% considered ARx app to be the most helpful resource in 2019, and the percent was significantly increased to 76.36% in 2020. Conclusion: AR technology implementation in pharmaceutical education could create student-centered engaging and interactive learning experience in fundamental areas such as pharmaceutical compounding laboratories.

Coronavirus disease (COVID-19) emerged in China in December 2019. In March 2020, the WHO declared it a pandemic leading to worldwide lockdowns and travel restrictions. By May, it infected 4,789,205 and killed 318,789 people. This led to severe shortages in the medical sector besides devastating socio-economic effects. Many technologies such as artificial intelligence (AI), virtual reality (VR), microfluidics, 3D printing, and 3D scanning can step into contain the virus and hinder its extensive spread. This article aims to explore the potentials of 3D printing and microfluidic in accelerating the diagnosis and monitoring of the disease and fulfilling the shortages of personal protective equipment (PPE) and medical equipment. It highlights the main applications of 3D printers and microfluidics in providing PPE (masks, respirators, face shields, goggles, and isolation chambers/hoods), supportive care (respiratory equipment) and diagnostic supplies (sampling swabs & lab-on-chip) to ease the COVID-19 pressures. Also, the cost of such technology and regulation considerations are addressed. We conclude that 3D printing provided reusable and low-cost solutions to mitigate the shortages. However, safety, sterility, and compatibility with environmental protection standards need to be guaranteed through standardization and assessment by regulatory bodies. Finally, lessons learned from this pandemic can also help the world prepare for upcoming outbreaks.

The aim of this work is to improve the overall healthcare experience of patients with Autism Spectrum Disorder (ASD), this study was conducted to collect the perspectives of healthcare professionals’ (mainly pharmacists) on current healthcare barriers for patients with ASD. The study aims to identify possible interventions to minimize the patient-provider communication gap, that takes in consideration the social skills and language/communication level of patients with ASD. The ultimate goal is improving the healthcare experience for patients on the spectrum and narrow the communication gap between adult patients with ASD and their trusted pharmacists. An online questionnaire was created using Google Forms and results were directly extrapolated into easy-to-read tables, and graphs. Questionnaire was sent to healthcare providers. All participants were kept anonymous, and de-identified. A total of 116 participants completed the online questionnaire. Most participants came from hospitals-inpatient, followed by community pharmacies, and hospitals-outpatient, and span across all years of practice. Responses from female providers were significantly higher. The majority of providers did not receive any additional training, and do not believe they are comfortable communicating and/or prepared to provide quality care to patients with ASD. Providers desire to bridge the gap and explore novel communication tools. Information from this study will be the seed to develop an innovative communication tool for transfer/exchange/retrieval of information between ASD patients and their providers. The communication aid will be piloted in the next phase of this research.

Objective: Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural. Methods: Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis. Results: HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter-and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects. Conclusion: Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers. Please cite this article as: Nounou MI, Eassa HA, Helal NA, AboulFotouh K, Mansoor I, Latz IK, Zheng C, Eassa HA, Mohamed D, Huynh DM, Wiss AR, Sweeney J, Oakes MT, Mikhail MM, Amine N, Kaur H, Echeverry N, Orzechowski K, Szollosi D. The safety, efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online: Truth versus claim. (C) 2021 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.

Phosphodiesterases (PDEs) represent a class of enzymes that act mainly on cAMP and cGMP. The value of these enzymes has been known for long time. Molecules that target PDEs have been used in various therapeutic applications. This review aims to explore the potential uses of PDE inhibitors (PDEIs) as therapeutic agents to treat conditions that extend beyond erectile dysfunction (ED), as well as highlight novel delivery methods for PDEIs. Keywords: Phosphodiesterase inhibitors; Alzheimer’s disease; Cognition; Psoriasis; Sildenafil

Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Inflammaging has recently emerged as a pathway that correlates aging and age-related diseases with inflammation. This review discusses the role and pathways of inflammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with inflammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier-based formulations. In recent years, consumers' demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the efficacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations.

Objective: To design a controlled topical delivery system of lornoxicam (LX) in order to enhance skin permeation and treatment efficacy. Nanosponges were selected as a novel carrier for this purpose. Methods: Nanosponges were formulated via the emulsion solvent evaporation method using ethyl cellulose (polymer) and polyvinyl alcohol (surfactant). Nanosponge dispersions were characterized for colloidal properties, entrapment efficiency and in vitro release study. The nanosponge formulation (LS1) was then incorporated into carboxymethyl cellulose sodium hydrogels and evaluated for pH, viscosity and in vitro drug release. Skin irritation was evaluated, and anti-inflammatory activity was assessed via rat hind paw edema method. Results: Nanosponges were in the nano-sized range and attained a uniform round shape with a spongy structure. LS1exhibited the highest LX release after 6 h, so it was incorporated as hydrogel. Formulated hydrogels showed acceptable physicochemical parameters (pH, drug content and rheological properties). Skin irritation testing proved LX-loaded nanosponge hydrogel formulation (G1) to be non-irritant. In vivo study revealed an enhanced anti-inflammatory activity of G1 for 6 h (p<0.001). Conclusion: The developed nanosponge hydrogel is an efficient nanocarrier for improved and controlled topical delivery of LX.

Continuous manufacturing (CM) has the potential to provide pharmaceutical products with better quality, improved yield and with reduced cost and time. Moreover, ease of scale-up, small manufacturing footprint and on-line/in-line monitoring and control of the process are other merits for CM. Regulating authorities are supporting the adoption of CM by pharmaceutical manufacturers through issuing proper guidelines. However, implementation of this technology in pharmaceutical industry is encountered by a number of challenges regarding the process development and quality assurance. This article provides a background on the implementation of CM in pharmaceutical industry, literature survey of the most recent state-of-the-art technologies and critically discussing the encountered challenges and its future prospective in pharmaceutical industry.