Design of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology. Probing of cellular internalisation pathways by a panel of pharmacological inhibitors indicated that clathrin-mediated (dynamin-dependent) endocytosis, macropinocytosis (dynamine independent), and cell membrane cholesterol dependent process(es) (clathrin and caveolea-independent) all play a role in the siRNA-liposomes internalization. The inhibition of either of these entry routes was, in general, mirrored by a reduction in the level of siRNA engagement with its target mRNA, as well as in a reduction of the target gene silencing. A dramatic increase in siRNA engagement with its target RNA was observed on disruption of endosomal membrane (by chloroquine), accompanied with an increased silencing. The work thus illustrates that employing molecular beacon siRNA technology one can start to assess the target RNA engagement – a stage between initial cellular internalization and final gene silencing of siRNA delivery systems.

Introduction: Urinary Tract Infections (UTIs) is one of the most common infections worldwide. UTIs remain a challenge to the healthcare system because of the emergence of antimicrobial resistance. The aim of this study is to report the most common UTI-causative organisms associated with the emergence of antimicrobial resistance in Saudi Arabia. Methodology: a retrospective cross sectional study of 1918 positive urine culture samples of both gender collected over 9 months (May 2015 to February 2016) from a major tertiary hospital in Riyadh, Saudi Arabia. Results: the median age of individuals involved in the study was 43 years, with males constituting 27.7% only of the population. Among cases deemed complicated (81.1%), common causes were diabetes, pregnancy, and immunocompromization, comprising 24.7%, 11.9%, and 10.8%, respectively.  Escherichia coli (52%) was the most common uropathogen, followed by Klebsiella pneumoniae (15%), Pseudomonas aeruginosa (8%) Streptococcus agalactiae (Group B streptococcus) (7%), and Enterococcus faecalis (5%). Overall sensitivity studies showed the most highly resistant uropathogen was Escherichia coli (60%) followed by Klebsiella pneumoniae (16%), Pseudomonas aeruginosa (4%) Enterococcus faecalis (3%), and Enterobacter cloacae (2%). Concerning the first defense antibiotics prescribed for UTI, E. coli was most frequently resistant to Sulfamethoxazole/Trimethoprim (47%) followed by ciprofloxacin (34%). K. pneumoniae was most frequently resistant to Sulfamethoxazole/trimethoprim (35%) followed by cefuroxime (30%), while P. aeruginosa to ciprofloxacin (13%). Conclusion: Because of a high level of antimicrobial resistance amongst uropathogens in Saudi Arabia, the development of regional and national UTI guidelines is recommended.

The emergence of phytosome nanotechnology has a potential impact in the field of drug delivery and could revolutionize the current state of topical bioactive phytochemicals delivery. The main challenge facing the translation of the therapeutic activity of phytochemicals to a clinical setting is the extremely low absorption rate and poor penetration across biological barriers (i.e., the skin). Phytosomes as lipid-based nanocarriers play a crucial function in the enhancement of pharmacokinetic and pharmacodynamic properties of herbal-originated polyphenolic compounds, and make this nanotechnology a promising tool for the development of new topical formulations. The implementation of this nanosized delivery system could enhance the penetration of phytochemicals across biological barriers due to their unique physiochemical characteristics, improving their bioavailability. In this review, we provide an outlook on the current knowledge of the biological barriers of phytoconstituents topical applications. The great potential of the emerging nanotechnology in the delivery of bioactive phytochemicals is reviewed, with particular focus on phytosomes as an innovative lipid-based nanocarrier. Additionally, we compared phytosomes with liposomes as the gold standard of lipid-based nanocarriers for the topical delivery of phytochemicals. Finally, the advantages of phytosomes in topical applications are discussed.

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.

Hand hygiene is an essential factor to prevent or minimize the spread of infections. The ability to prepare an alcohol-free hand sanitizer (AFHS) with antimicrobial properties is crucial, especially during pandemics, when there are high demands and a low supply chain for ethanol and isopropanol. The objective of this study was to prepare AFHS gels based on natural materials that contain essential oils (EOs) that would be effective against a broad spectrum of pathogens. The results showed that the organoleptic characteristics of all prepared hand sanitizer gels were considered acceptable. The pH of the formulations was slightly acidic (circa 3.9) owing to the presence of aloe vera in large proportions (90% v/v), which is known for its acidity. The spreadability for all tested formulations was in the acceptable range. The antimicrobial effectiveness test demonstrated that the prepared hand sanitizer gels had antimicrobial activities against different gram-positive and gram-negative bacteria and Candida albicans yeast. The highest antibacterial effect was observed with tea tree oil hand sanitizers, which lack activity against the yeast, while clove oil hand sanitizers showed effectiveness against all microorganisms, including Candida albicans. The lavender hand sanitizer exhibited the least antimicrobial efficiency. The acceptability study on 20 human volunteers showed that the hand sanitizer gel containing 1.25% (v/v) clove oil did not produce any signs of skin irritation. This study suggested that the prepared natural hand sanitizer gel with 1.25% (v/v) clove oil can be a potential alternative to commonly used alcohol-based hand sanitizers (ABHS).