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The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol ® 888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly ( p  < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.

RNAs are known for versatile functions and therapeutic utility. They have gained significant interest since the approval of several RNA drugs, including COVID-19 mRNA vaccines and therapeutic agents targeting liver diseases. There are increasing expectations for a new class of RNA drugs for broader applications. Successful development of RNA drugs for new applications hinges on understanding their diverse functions and structures. In this review, we explore the last five years of literature to understand current approaches to formulate a spectrum of RNA drugs, focusing on new efforts to expand their applications beyond vaccines and liver diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of -44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly ( p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma.

Background: Acute myeloid leukemia (AML) is a diverse disease characterized by the expansion of blasts of myeloid lineage. Cytogenetic testing is the cornerstone for risk stratification of AML patients. Geographical and environmental factors may play a very important role in the development of leukemia and several differences in genetic profile may be seen among different ethnicities. In our study, we evaluated cytogenetic findings of adult AML patients in South Egypt., Methods: Cytogenetic testing (karyotyping and M-FISH) was performed for 120 adult patients with AML. Twenty metaphases were analyzed for each patient., Results: In our study, the median age of AML patients was 36.5 years, with an age range between 18 and 86 years. 56.7% of patients had normal karyotypes and 43.3% of patients had clonal cytogenetic abnormalities. t (15;17) was the most detected structural abnormality, and + 8 was the most detected numerical abnormality. Regarding cytogenetic risk stratification, 65% of patients were in the intermediate-risk category., Conclusion: The cytogenetic profile of AML patients in our locality showed some differences and some similarities with cytogenetic profiles in different Arab, Asian and Western countries. Further studies are needed using advanced techniques such as next-generation sequencing and optical genome mapping to elucidate more ethnic and geographic genetic heterogeneity among different countries., (© 2022. The Author(s).)

The outcome for chronic phase (CP) chronic myelogenous leukemia (CML) patients has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. We examined the characteristics of CML patients during TKI therapy by determining the plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), and transforming growth factor (TGFβ1) biomarkers. The plasma levels of sVCAM-1 and TGFβ1 were measured by ELISA at baseline and after 3 months of TKI treatment. The levels of sVCAM-1, and TGFβ1 were significantly elevated in patients with CML (P< 0.01). Dasatinib treatment was associated with a significant reduction in the levels of these biomarkers (P< 0.01). In conclusion, plasma levels of sVCAM-1 and TGFβ1 could have a role in the pathogenesis of CML and may be used as predictors of hematological and molecular responses to TKIs. A favorable outcome for Dasatinib therapy was observed., (Copyright© by the Egyptian Association of Immunologists.)

Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor-positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators-Tween 80, Brij 35, and Cremophor RH40-with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129-310 nm and 240-560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3-97.2% and 97.9-99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.

The main objective of this project was to formulate novel decorated amphiphilic PLGA nanoparticles aiming for the selective delivery of the novel peptide (CK-10) to the cancerous/tumor tissue. Novel modified microfluidic techniques were used to formulate the nanoparticles. This technique was modified by using of Nano Assemblr associated with salting out of the organic solvent using K 2 HPO 4 . This modification is associated with higher peptide loading efficiencies, smaller size and higher uniformity. Size, zeta potential & qualitative determination of the adsorbed targeting ligands were measured by dynamic light scattering and laser anemometry techniques using the zeta sizer. Quantitative estimation of the adsorbed targeting ligands was done by colorimetry and spectrophotometric techniques. Qualitative and quantitative uptakes of the various PLGA nanoparticles were examined by the fluorescence microscope and the flow cytometer while the cytotoxic effect of the nanoparticles was measured by the colorimetric MTT assay. PLGA/poloxamer.FA, PLGA/poloxamer.HA, and PLGA/poloxamer.Tf have breast cancer MDA. MB321 cellular uptakes 83.8, 75.43 & 69.37 % which are higher than those of the PLGA/B cyclodextrin.FA, PLGA/B cyclodextrin.HA and PLGA/B cyclodextrin.Tf 80.87, 74.47 & 64.67 %. Therefore, PLGA/poloxamer.FA and PLGA/poloxamer.HA show higher cytotoxicity than PLGA/ poloxamer.Tf with lower breast cancer MDA-MB-231 cell viabilities 30.74, 39.15 & 49.23 %, respectively. The design of novel decorated amphiphilic CK-10 loaded PLGA nanoparticles designed by the novel modified microfluidic technique succeeds in forming innovative anticancer formulations candidates for therapeutic use in aggressive breast cancers., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages, but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is an inflammatory autoimmune polyarthritis with progressive destruction of the synovial joints associated with systemic manifestations. RA is characterized by infiltration of the synovial joints with inflammatory immune cells with premature immunosenescence. Shorter telomere length in the peripheral blood cells and increase in the oxidative stress have been detected in patients with RA. The aim of the present study was to study the association of markers of telomere shortening and oxidative stress with RA disease activity. Sixty-one RA patients and 15 healthy controls were enrolled in the study. Demographic data, clinical examination, and disease activity status were evaluated for the RA patients. Serum levels of chitinase and NAG (telomere markers) were determined by biochemical reactions using colloidal chitin and NAG as substrates, respectively. Nitric oxide and superoxide dismutase (oxidative stress markers) were determined colometrically and spectrophotometrically, respectively, in the sera of RA patients and controls. Results were correlated with disease activity. Indices of telomere shortening and oxidative markers were significantly higher in RA patients compared to controls. These indices were correlated with signs of disease activity (including number of swollen and tender joints, DAS-28, and inflammatory markers). Rheumatoid arthritis is a disease in which markers of telomere shortening and elevated oxidant stress correlate with disease activity.