The solubility and solution thermodynamic properties of a “bioactive nutraceutical” sinapic acid (SA) in different “2-(2-ethoxyethoxy)ethanol (Carbitol
®
) + water” mixtures were investigated. The ...“mole fraction solubilities (
x
e
)” of SA in various “Carbitol + water” systems were determined at “
T
= 298.15–318.15 K” and “
p
= 0.1 MPa.” The measured
x
e
values of SA were found well regressed by “Apelblat, van’t Hoff, Yalkowsky, Jouyban–Acree and Jouyban–Acree–van’t Hoff” models with mean percent deviations of < 4.0%. The maximum
x
e
value of SA was recorded in pure Carbitol (4.15 × 10
−2
at
T
= 318.15 K), and the minimum one was estimated in neat water (6.28 × 10
−5
at
T
= 298.15 K). The regressed results were found to be in accordance with experimental results of SA. Using activity coefficients, mixing thermodynamic parameters of SA were determined. The results showed spontaneous dissolution of SA in most of the cosolvent mixtures.
This study aimed to enhance the hepatic targeting of 5‐fluorouracil (5‐FU) by tyloxapol (TYL) and nanoliposomes to promote drug efficacy and safety. The lipophilicity of 5‐FU was increased by ...cholesterol conjugation (5‐FUC). Nanoliposomes were prepared, characterized, and loaded with 5‐FU and 5‐FUC and injected into TYL‐treated male Wistar albino rats. After 4 h, LDL and hepatic homogenate were isolated, and the concentrations of 5‐FU and 5‐FUC were investigated in both specimens. The pharmacokinetic parameters of 5‐FU‐ and 5‐FUC‐loaded liposomes were also investigated. The present results revealed that the prepared liposomes have a nanoscale size, negative zeta potential, and prolonged drug release. TYL injection significantly elevated the plasma levels of nonhigh‐density lipoproteins, triacylglycerol (TAG), and total cholesterol (TC). The isolated LDL nanoparticles had a nanosized homogenous vesicle structure and a negative zeta potential. 5‐FUC‐loaded liposomes and TYL augmented 5‐FUC loading into LDL and hepatic tissues compared to that for 5‐FU. Moreover, the present results indicated that 5‐FUC‐loaded liposomes significantly improved the Cmax, Tmax, AUC, MRT, and t1/2 compared to those for the 5‐FUC solution and 5‐FU‐loaded liposomes. This study concluded that the triple approach of a lipophilic shift, nanoliposomes, and TYL is promising for enhancing drug bioavailability, LDL loading, and selective hepatic drug targeting.
Practical Applications: 5‐Fluorouracil (5‐FU) is a hydrophilic anticancer medicine that elicits multiple side effects due to high doses, short half‐life, and nonspecific tissue distribution. In this study, 5‐FU was shifted into a lipophilic form (5‐FUC) by cholesterol conjugation. The 5‐FUC was loaded into a nanoliposome. Rats were injected with tyloxapol (TYL) to induce a temporary hyperlipidemia that produces a lipophilic milieu. The hyperlipidemia was confirmed physically by plasma milky appearance and biochemically by marked elevation of non‐HDL lipoproteins. Hyperlipidemia promotes 5‐FUC loading into VLDL‐LDL in vivo. The 5‐FUC level was determined in isolated LDL and liver tissues using HPLC analysis. The lipophilic shift, liposomal loading, and TYL improve pharmacokinetic parameters and bioavailability of 5‐FU with sustained action and hepatic targeting. This study opens a new avenue for endogenous drugs loading into lipoproteins as an approach for selective hepatic drug targeting.
Tyloxapol induces elevation of LDL/VLDL. Injection of the free and loaded drug (5‐FUC). Increase LDL drug loading and hepatic targeting.
Gene editing technologies (GETs) could induce gene knockdown or gene knockout for biomedical applications. The clinical success of gene silence by RNAi therapies pays attention to other GETs as ...therapeutic approaches. This review aims to highlight GETs, categories, mechanisms, challenges, current use, and prospective applications. The different academic search engines, electronic databases, and bibliographies of selected articles were used in the preparation of this review with a focus on the fundamental considerations. The present results revealed that, among GETs, CRISPR/Cas9 has higher editing efficiency and targeting specificity compared to other GETs to insert, delete, modify, or replace the gene at a specific location in the host genome. Therefore, CRISPR/Cas9 is talented in the production of molecular, tissue, cell, and organ therapies. Consequently, GETs could be used in the discovery of innovative therapeutics for genetic diseases, pandemics, cancer, hopeless diseases, and organ failure. Specifically, GETs have been used to produce gene-modified animals to spare human organ failure. Genetically modified pigs are used in clinical trials as a source of heart, liver, kidneys, and lungs for xenotransplantation (XT) in humans. Viral, non-viral, and hybrid vectors have been utilized for the delivery of GETs with some limitations. Therefore, extracellular vesicles (EVs) are proposed as intelligent and future cargoes for GETs delivery in clinical applications. This study concluded that GETs are promising for the production of molecular, cellular, and organ therapies. The use of GETs as XT is still in the early stage as well and they have ethical and biosafety issues.
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This study aims to highlight the potential use of cTNAs in therapeutic applications. The COVID-19 pandemic has led to significant use of coding therapeutic nucleic acids (cTNAs) in terms of DNA and ...mRNA in the development of vaccines. The use of cTNAs resulted in a paradigm shift in the therapeutic field. However, the injection of DNA or mRNA into the human body transforms cells into biological factories to produce the necessary proteins. Despite the success of cTNAs in the production of corona vaccines, they have several limitations such as instability, inability to cross biomembranes, immunogenicity, and the possibility of integration into the human genome. The chemical modification and utilization of smart drug delivery cargoes resolve cTNAs therapeutic problems. The success of cTNAs in corona vaccine production provides perspective for the eradication of influenza viruses, Zika virus, HIV, respiratory syncytial virus, Ebola virus, malaria, and future pandemics by quick vaccine design. Moreover, the progress cTNAs technology is promising for the development of therapy for genetic disease, cancer therapy, and currently incurable diseases.
Graphical Abstract
This topical review digs into special education teachers' growing usage of Assistive Technology (AT) in Arabic-speaking countries to serve children with impairments. This study investigates AT's ...benefits, drawbacks, and possible applications in this educational setting by reviewing the available literature from six major academic databases, including Scopus, Web of Science, JSTOR, ERIC, Academia, and ResearchGate. The findings highlight the need for tailored and student-centered approaches to AT adoption and effective training and ongoing support for educators and students. Furthermore, the study emphasizes the potential of AT to improve academic and functional outcomes, allowing students to overcome obstacles and actively participate in their educational path. The significance of these findings for future special education research and practice is examined, laying the groundwork for further investigation of AT's influence on children with disabilities in Arabic-speaking countries. The outcomes of this review emphasize the need to implement AT in Arabic-speaking special education settings using tailored and student-centered approaches. Students with disabilities can effectively use AT solutions to enhance their learning experiences by tailoring AT solutions to specific needs. Furthermore, the study emphasizes the importance of instructor and student training and ongoing assistance. Proper training provides instructors with the skills and information they need to properly deploy AT tools, while continual support ensures that AT remains effective in the classroom.
Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of ...this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including the surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with a low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta potential, and drug EE of the prepared micelles were all measured. The in vitro drug release profiles were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7 nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (
< 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm
/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. In summary, Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin-modifying enhancers.
Generic medications are cost-effective without compromising therapeutic outcomes. Therefore, the goal of this study was to investigate, using a cross-sectional study design, the factors influencing ...Saudi Arabian consumers' preferences between innovator and generic medications.
This cross-sectional study was carried out in Saudi Arabia using a Google survey form. For data collection, a simple random sampling strategy was used. The recruited participants were surveyed using a validated questionnaire that focused on six influencing domains: physician, pharmacist, perceived effectiveness, price, information availability, and confidence based on prior experience. The obtained data was used to analyze factors that have an association with any of the six domains using multinomial regression analysis. A correlation analysis was performed to examine the relationship between domains.
The 317 participants included 64.4 % females, 52 % aged ≥ 26, and a large proportion of Saudi nationals (82.6 %) and university graduates (78.9 %). Being employed (OR:3.029; P = 0.006; CI: 6.715–1.366), a healthcare providers (OR:2.298; P = 0.043; CI: 5.151–1.025), and having insurance coverage (OR:1.908; P = 0.017; CI: 3.245–1.122) had a greater influence on medication selection. Participants with linguistic and business educational backgrounds (OR:3.443; P = 0.022; CI: 9.950–1.191), those living in the northern region of Saudi Arabia (OR:3.174; P = 0.009; CI: 7.585–1.328), having chronic ailments (OR:3.863; P = 0.013; CI: 11.274–1.324), and possess insurance (OR:1.748; P = 0.039; CI: 2.971–1.028) get readily influenced by pharmacist. People who were married and lived in Saudi Arabia's southern region were influenced by perceived effectiveness when choosing medicine. Participants from the northern region were found to be influenced by the price of the medicines, information about the medicines, and confidence based on previous experience. The price of medicines has a significant impact on those suffering from chronic diseases. At a significant level of P = 0.01, all six influencing domains were found to be positively correlated with each other.
The study shows that healthcare providers, drug prices, perceived efficacy, and information availability all have a big influence on the Saudi Arabian population's choice of medications.Educational background, location, and chronic disease status are associated with several influencing domains. Aside from public awareness campaigns, healthcare professionals should be involved in the implementation of the generic medication policy.
The elderly population is affected by chronic diseases and lifelong medication. The American Geriatrics Society (AGS) Beers Criteria is a comprehensive approach to medication usage in the older ...population to reduce potentially inappropriate medication (PIM) use. The purpose of this study was to assess the usage of PIMs in elderly patients upon discharge from tertiary care hospital settings in Riyadh, Saudi Arabia, using the AGS Beers Criteria 2019.
The data was obtained from the medical records of 1237 patients (>65 years) who were discharged from medical or surgical wards at two hospitals affiliated with King Abdulaziz Medical City. The data was analyzed to determine the prevalence of PIM prescription, and the proportional odds of the independent factors influencing outcomes were estimated using ordinal regression analysis for criteria 1 and 2, while Binary regression analysis was conducted for criterion 3.
There were approximately equal numbers of male and female participants in our study (male: 50.8 % vs. female: 49.2 %). One-third of the patients were above the age of 80 years, with 41 % being between the ages of 70 and 80 years. Moreover, almost 70 % of the samples had chronic illnesses. The overall prevalence of PIMs was 29.2 %, with 11 % of PIMs to be avoided in elderly patients and 17 % to be used with caution in the elderly, while disease-specific PIMs were identified in 1.2 % of the patients. The most common PIM class was proton pump inhibitors (44.41 %), and patients discharged from the surgical unit were more likely to be prescribed PIMs. Proton pump inhibitors (44.41 %) were the most inappropriately prescribed drug class, and patients discharged from the surgical unit were more likely to be prescribed PIMs.
The study noticed that male gender, the presence of multiple diseases, and obesity are associated with more than one PIM prescription. There is a need to streamline the surgical department’s prescription procedure to eliminate prescription disparities. Prescription monitoring is recommended to avoid medication errors, particularly in patients who are taking multiple medications.
This study aimed to assess dentists' views of the utility of an unrestored shortened dental arch (SDA) compared to the utility of various prosthetic treatment options.
A total of 142 dentists working ...at four sites in Riyadh, Saudi Arabia, were interviewed and presented with 18 scenarios for patients of different ages with SDAs that lost molar teeth. Participants were asked to indicate on a standardized visual analog scale (VAS) how they would value the health of the patient's mouth if the SDAs were left unrestored or restored with five prosthetic dental restorations.
With a utility value of 0.0 representing the worst possible health state for a mouth and 1.0 representing the best, dentists' mean utility value for unrestored SDAs was 0.43 (standard deviation SD = 0.28). For implant-supported fixed dental prostheses (ISFDPs), cobalt-chromium removable partial dentures (RPDs), acrylic RPDs, cantilever conventional fixed dental prostheses (CFDPs), and cantilever resin-bonded fixed dental prostheses (RBFDPs), the mean utility values were 0.64 (SD = 0.27), 0.54 (SD = 0.20), 0.48 (SD = 0.20), 0.42 (SD = 0.28), and 0.39 (SD = 0.27), respectively. Neither patient age nor dentists' clinical experience had an impact on dentists' perceptions of the utility of unrestored SDAs and outcomes of this treatment concept (P > .01).
Restoration of SDAs by ISFDPs received the highest utility value among the surveyed group of dentists. Although the assigned value for unrestored SDAs was low, this value was comparable to the value of SDAs that were restored by acrylic RPDs or cantilever FDPs of either type.
Despite substantial investments in anti-glioblastoma (GBM) drug discovery over the last decade, progress is limited to preclinical stages, with clinical studies frequently encountering obstacles. ...Angiogenic and histone deacetylase inhibitors (HDACi) have shown profound results in pre-clinical studies. Investigating a multicomponent anti-cancer remedy that disrupts the tumor angiogenic blood vessels and simultaneously disrupts HDACs, while inducing minimal side effects, is critically needed. The crude extracts derived from medicinal plants serve as a renewable reservoir of anti-tumor drugs, exhibiting reduced toxicity compared to chemically synthesized formulations. Calotropis procera is a traditional medicinal plant, and its anticancer potential against many cancer cell lines has been reported, however its antiangiogenic and HDAC inhibitory action is largely unknown. The anticancer activity of methanol leaf extract of C. procera was tested in three types of human glioblastoma cell lines. Wild-type and transgenic zebrafish embryos were used to evaluate developmental toxicity and angiogenic activity. A human angiogenic antibody array was used to profile angiogenic proteins in the U251 GM cell line. A real-time reverse transcriptase polymerase chain reaction (RT PCR) assay was used to detect the differential expression of eleven HDAC genes in U251 cells treated with C. procera extract. The extract significantly reduced the proliferation of all three types of GBM cell lines and the cytotoxicity was found to be more pronounced in U251 GM cells, with an IC50 value of 2.63 ± 0.23 μg/ml, possibly by arresting the cell cycle at the G2/M transition. The extract did not exhibit toxic effects in zebrafish embryos, even at concentrations as high as 1000 μg/ml. The extract also inhibited angiogenic blood vessel formation in the transgenic zebrafish model in a dose-dependent manner. The results from the angiogenic antibody array have suggested novel angiogenesis targets that can be utilized to treat GBM. Real-time RT PCR analysis has shown that C. procrea extract caused an upregulation of HDAC5, 7, and 10, while the mRNA of HDAC1, 2, 3 and 8 (Class I HDACs), and HDAC4, 6, and 9 (Class II) were downregulated in U251 GM cells. The cytotoxicity of the C. procera extract on GBM cell lines could be due to its dual action by regulation of both tumor angiogenesis and histone deacetylases enzymes. Through this study, the C. procera leaf extract has been suggested as an effective remedy to treat GBM with minimal toxicity. In addition, various novel angiogenic and HDAC targets has been identified which could be helpful in designing better therapeutic strategies to manage glioblastoma multiforme in human patients.
