TARGETED DUAL FUNCTIONAL NANOPARTICLES FOR THE TREATMENT OF CANCER AND LIVER FIBROSIS

For decades, a large number of therapeutics have been discovered and developed with high potential for curing various diseases, many of which have been clinically used for years. However, some treatments are greatly limited due to their side effects, which arise from their inability to differentiate between normal and diseased cells. The aim of this dissertation work is to develop nanomaterial-based dual function drug delivery systems to improve overall therapeutic outcomes for the treatment of cancer and liver fibrosis. The first part of this work focused on the development of FTS-based solid lipid nanoparticles (SLNs) for cancer-targeted delivery of paclitaxel (PTX). Novel SLNs were successfully developed which are capable of solubilizing PTX while simultaneously avoiding unwanted side effects of the clinically used PTX formulation (Taxol). The data from this study demonstrated that the PTX-SLNs system has a significantly improved profile in terms of controlled release kinetics and stability compared to Taxol. Additionally, PTX-SLNs have shown enhanced anticancer activity in vivo. The second part focused on improved delivery of the herbal agent thymoquinone (TQ) to hepatic stellate cells (HSCs) for the treatment of liver fibrosis. Firstly, a study was conducted on the biological effects of TQ on HSCs, which represent the major liver cell type involved in the massive production of extra cellular matrix (ECM) in liver fibrosis. The results revealed that TQ exerts hepatoprotective and anti-fibrotic effects via direct inhibition of the fibrogenic activities of HSCs, which suggests that TQ holds great potential as a new drug candidate for treatment of liver fibrosis. Secondly, an examination was conducted on the potential of a novel dual functional micellar system PEG5k-Fmoc-FTS2 to deliver TQ into activated HSCs in vitro. TQ-micelles have shown high tolerability in activated HSCs with more efficient anti-fibrotic activity compared to free TQ. Collectively, this work suggests that an FTS-based SLNs system represents a promising nanocarrier for cancer-targeted delivery which could enhance the therapeutic efficiency of anticancer agents. In addition, TQ holds a great a potential as new therapy for the treatment of liver fibrosis, and formulating TQ into the PEG5k-Fmoc-FTS2 micelles system could further enhance overall anti-fibrotic activity

Adherence to antidiabetic medication during the month of Ramadan among diabetes mellitus patients in the kingdom of Saudi Arabia

Background: Ramadan may lead to reduced adherence to antidiabetic medications among Saudi diabetes patients due to fasting, changes in daily routine, social and cultural influences, health risks, and inadequate awareness. This study aimed to assess the Saudi population adherence to the diabetes management medication in Ramadan. Methodology: A convenience sampling method was used to recruit participants for the study. Participants were sourced from social media platforms, diabetes mellitus patient groups, and healthcare providers groups. The Medication Adherence Rating Scale (MARS), a tool, was used to assess medication compliance. Results: A total of 384 individuals were included in this study, 20.3% were from Riyadh, 52.3% were males, 35% aged 31-50 years, and 64.1% had type 2 diabetes mellitus of participants. Age between 31-50 years was negatively associated with compliance (β = -1.06, p = 0.002), while age between 51-65 years is positively associated ((β= 1.00, p = 0.003). Being male was negatively associated with compliance (β= -0.72, p = 0.001). Different fasting behaviors like non-fasting one day or more (β = -2.92, p < 0.001) and fasting all month (β = -2.90, p < 0.001), significantly affect compliance scores with negative associations indicating lower compliance during fasting periods. Various HbA1c levels were significant predictors of compliance. Higher HbA1c levels were associated with increased compliance. Conclusions: The study reveals that age, gender, fasting behaviors and HbA1c levels significantly impact medication compliance among patients with diabetes mellitus during Ramadan

Computational intelligence modeling of hyoscine drug solubility and solvent density in supercritical processing: gradient boosting, extra trees, and random forest models

Abstract This work presents the results of using tree-based models, including Gradient Boosting, Extra Trees, and Random Forest, to model the solubility of hyoscine drug and solvent density based on pressure and temperature as inputs. The models were trained on a dataset of hyoscine drug with known solubility and density values, optimized with WCA algorithm, and their accuracy was evaluated using R2, MSE, MAPE, and Max Error metrics. The results showed that Gradient Boosting and Extra Trees models had high accuracy, with R2 values above 0.96 and low MAPE and Max Error values for both solubility and density output. The Random Forest model was less accurate than the other two models. These findings demonstrate the effectiveness of tree-based models for predicting the solubility and density of chemical compounds and have potential applications in determination of drug solubility prior to process design by correlation of solubility and density to input parameters including pressure and temperature

QbD-Optimized, Phospholipid-Based Elastic Nanovesicles for the Effective Delivery of 6-Gingerol: A Promising Topical Option for Pain-Related Disorders

In this study, elastic nanovesicles, constructed of phospholipids optimized by Quality by Design (QbD), release 6-gingerol (6-G), a natural chemical that may alleviate osteoporosis and musculoskeletal-related pain. A 6-gingerol-loaded transfersome (6-GTF) formulation was developed using a thin film and sonication approach. 6-GTFs were optimized using BBD. Vesicle size, PDI, zeta potential, TEM, in vitro drug release, and antioxidant activity were evaluated for the 6-GTF formulation. The optimized 6-GTF formulation had a 160.42 nm vesicle size, a 0.259 PDI, and a −32.12 mV zeta potential. TEM showed sphericity. The 6-GTF formulation’s in vitro drug release was 69.21%, compared to 47.71% for the pure drug suspension. The Higuchi model best described 6-G release from transfersomes, while the Korsmeyer–Peppas model supported non-Fickian diffusion. 6-GTF had more antioxidant activity than the pure 6-G suspension. The optimized transfersome formulation was converted into a gel to improve skin retention and efficacy. The optimized gel had a spreadability of 13.46 ± 4.42 g·cm/s and an extrudability of 15.19 ± 2.01 g/cm2. The suspension gel had a 1.5 μg/cm2/h ex vivo skin penetration flux, while the 6-GTF gel had 2.71 μg/cm2/h. Rhodamine B-loaded TF gel reached deeper skin layers (25 μm) compared to the control solution in the CLSM study. The gel formulation’s pH, drug concentration, and texture were assessed. This study developed QbD-optimized 6-gingerol-loaded transfersomes. 6-GTF gel improved skin absorption, drug release, and antioxidant activity. These results show that the 6-GTF gel formulation has the ability to treat pain-related illnesses effectively. Hence, this study offers a possible topical treatment for conditions connected to pain

Pharmacy students’ perceptions towards online learning in a Saudi Pharmacy School

Objectives: The aim of the study was to evaluate previous exposure to online learning and preference for learning through pre-recorded online lectures with or without live active learning among pharmacy students in their fifth year. Methods: An anonymous online survey was self-administered to fifth-year students enrolled on the Graduation Research Project Course. Results: The response rate was 100%. Ninety-seven percent of students had previous experience with at least one online course during their pharmacy undergraduate curriculum; 76% of the courses were science courses. The majority of respondents preferred face-to-face, in-class lectures to online lectures, but 17% expressed no preference. Conclusion: Pharmacy students expressed some interest in online learning methods within the pharmacy curriculum. Keywords: Saudi Arabia, Online learning, Pharmacy, Education, King Khalid Universit

Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy–entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2–318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van’t Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsly–Roseman, Jouyban–Acree, and van’t Hoff–Jouyban–Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10−2) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10−6) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization

Solubility Determination, Hansen Solubility Parameters and Thermodynamic Evaluation of Thymoquinone in (Isopropanol + Water) Compositions

This article studies the solubility, Hansen solubility parameters (HSPs), and thermodynamic behavior of a naturally-derived bioactive thymoquinone (TQ) in different binary combinations of isopropanol (IPA) and water (H2O). The mole fraction solubilities (x3) of TQ in various (IPA + H2O) compositions are measured at 298.2–318.2 K and 0.1 MPa. The HSPs of TQ, neat IPA, neat H2O, and binary (IPA + H2O) compositions free of TQ are also determined. The x3 data of TQ are regressed by van’t Hoff, Apelblat, Yalkowsky–Roseman, Buchowski–Ksiazczak λh, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models. The maximum and minimum x3 values of TQ are recorded in neat IPA (7.63 × 10−2 at 318.2 K) and neat H2O (8.25 × 10−5 at 298.2 K), respectively. The solubility of TQ is recorded as increasing with the rise in temperature and IPA mass fraction in all (IPA + H2O) mixtures, including pure IPA and pure H2O. The HSP of TQ is similar to that of pure IPA, suggesting the great potential of IPA in TQ solubilization. The maximum molecular solute-solvent interactions are found in TQ-IPA compared to TQ-H2O. A thermodynamic study indicates an endothermic and entropy-driven dissolution of TQ in all (IPA + H2O) mixtures, including pure IPA and pure H2O

Development of Duloxetine Hydrochloride Tablets for Delayed and Complete Release Using Eudragit L 100

The purpose of the research was to optimize the preparation of duloxetine hydrochloride (duloxetine HCl) delayed release tablets. Duloxetine HCl produces a toxic substance called alpha-naphthol when duloxetine HCl is in contact with gastric fluid. Thus, duloxetine HCl when given orally needed a protective enteric coating that disable the delivery of duloxetine HCl in gastric fluid while enabling the drug delivery only in small intestine. Four different core tablets were prepared by direct compression technique, and the one which displayed quick disintegration and dissolution was chosen for enteric coating. The compressed tablets were enteric coated by dip coating technique. Since subcoating is required to safeguard the enteric coating, the core tablets were subcoated by using polymer HPMC K15M and then enteric coated with Eudragit L 100. The prepared tablets were assessed for the entire precompression and postcompression characteristics. FTIR study revealed the existence of all prominent peaks signifying its compatibility and authenticity. The in vitro studies showed that enteric-coated tablets were capable of restricting release in acidic media. The formulation F8 was optimised with 5% and 15% increase in weight of seal coat and enteric coat with good dissolution profile. Stability studies revealed that the optimized formulation was intact without any deterioration for 3 months. In conclusion, the optimized formulation could resist the drug release in acidic environment of gastrointestinal region and release the drug at a time once the tablet reaches the intestine

Antibacterial evaluation of 2-(6-Chloro-2-p-tolylquinazolin-4-ylthio) acetonitrile against pathogenic bacterial isolates with special reference to biofilm formation inhibition and anti-adherence properties

Background: Evaluating the effectiveness of a specific quinazoline molecule with antibacterial activity on microorganisms as a potential antibiotic substitution. Methods: A variety of microorganisms were tested with the designated quinazoline molecule. Differences within two groups were analyzed using the two-tailed Student’s t-test,. Results: Susceptibility tests revealed that the chemical has stronger antibacterial action against S. saprophyticus than other isolates, with just a slight effect on E. coli and M. smegmatis. The bacterial cells were subjected to varying concentrations of a certain molecule, and the results showed that the inhibition of bacterial adhesion was not consistent. This suggests that the effect of the molecule on bacterial adhesion is dependent on its concentration. After 24 h of treatment with varying chemical doses, all of the periodontal bacterial strains examined showed considerable inhibition of biofilm formation. Conclusions: According to the findings, the chemical molecule quinazoline could be utilized as an alternative therapeutic approach for microorganism-caused infections

Pharmacological Means of Pain Control during Separator Placement:A Systematic Review

AIM: To assess the effectiveness of adjuvant analgesics/anesthetics in pain control after separator placement compared with no medication. BACKGROUND: Separator placement to create space for cementing bands is the first clinical procedure done in orthodontics. Pain in this stage can negatively affect patient compliance and trust in the clinician. To date, there is no universally accepted regimen for pain control. MATERIALS AND METHODS: Electronic databases of PubMed, Scopus, and Web of Science were searched. One hundred and thirty-two potentially relevant studies were found. A total of eight randomized clinical trials including 642 subjects were selected. Data were extracted into customized forms, and selected studies were assessed for risk of bias using the Joanna Briggs Institute. RESULTS: Results showed the use of analgesics led to lower reported pain scores at almost all time intervals. NSAIDs resulted in a statistically significant reduction in pain compared to a control group. CONCLUSION: According to the available literature, the use of analgesics is effective in controlling orthodontic pain due to separators. Acetaminophen and ibuprofen show a stable analgesic effect. CLINICAL IMPLICATION: Acetaminophen 650 mg or ibuprofen 400 mg taken 1 hour prior to separator placement can reduce pain associated with the procedure