Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

Smart/stimuli-responsive chitosan/gelatin and other polymeric macromolecules natural hydrogels vs. synthetic hydrogels systems for brain tissue engineering: A state-of-the-art review.

Currently, there are no viable curative treatments that can enhance the central nervous system's (CNS) recovery from trauma or illness. Bioengineered injectable smart/stimuli-responsive hydrogels (SSRHs) that mirror the intricacy of the CNS milieu and architecture have been suggested as a way to get around these restrictions in combination with medication and cell therapy. Additionally, the right biophysical and pharmacological stimuli are required to boost meaningful CNS regeneration. Recent research has focused heavily on developing SSRHs as cutting-edge delivery systems that can direct the regeneration of brain tissue. In the present article, we have discussed the pathology of brain injuries, and the applicable strategies employed to regenerate the brain tissues. Moreover, the most promising SSRHs for neural tissue engineering (TE) including alginate (Alg.), hyaluronic acid (HA), chitosan (CH), gelatin, and collagen are used in natural polymer-based hydrogels and thoroughly discussed in this review. The ability of these hydrogels to distribute bioactive substances or cells in response to internal and external stimuli is highlighted with particular attention. In addition, this article provides a summary of the most cutting-edge techniques for CNS recovery employing SSRHs for several neurodegenerative diseases.

miRNAs driving diagnosis, prognosis and progression in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive form of skin malignancy with a high recurrence commonly within two to three years of initial diagnosis. The incidence of MCC has nearly doubled in the past few decades. Options for diagnosing, assessing, and treating MCC are limited. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play an important role in controlling many different aspects of cell biology. Many miRNAs are aberrantly expressed in distinct types of cancer, with some serving as tumor suppressors and others as oncomiRs. Therefore, the future holds great promise for the utilization of miRNAs in enhancing diagnostic, prognostic, and therapeutic approaches for MCC. Accordingly, the goal of this article is to compile, summarize, and discuss the latest research on miRNAs in MCC, highlighting their potential clinical utility as diagnostic and prognostic biomarkers.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

miRNAs driving diagnosis, progression, and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.

Chitosan coated clove oil-based nanoemulsion: An attractive option for oral delivery of leflunomide in rheumatoid arthritis.

Rheumatoid arthritis (RA), a distressing inflammatory autoimmune disease, is managed mainly by Disease-modifying antirheumatic drugs (DMARDs), e.g. leflunomide (LEF). LEF (BCS class II) has limited solubility and adverse effects following its systemic exposure. The appealing antirheumatic properties of both clove oil and chitosan (CS) were exploited to design oral leflunomide (LEF)-loaded nanoemulsion (NE) system to augment the therapeutic action of LEF and decrease its systemic side effects as well. Different LEF-NEs were prepared using clove oil, Tween® 20 (surfactant), and PEG 400(co-surfactant) and characterized by thermodynamic stability, percentage transmittance, cloud point, size analysis, and drug content. Optimized LEF-NE was subjected to CS coating forming LEF-CS-NE that exhibited nanometric size range, prolonged drug release, and good physical stability. In vivo anti-rheumatic activity of pure LEF, market LEF, and LEF-CS-NE was assessed utilizing a complete Freund's adjuvant (CFA) rat model. Treatment with LEF-CS-NE reduced edema rate (48.68% inhibition) and caused a marked reduction in interleukin-6 (IL-6) (510.9 ± 2.48 pg/ml), tumor necrosis factor- α (TNF-α) (397.3 ± 2.53 pg/ml), and rheumatoid factor (RF) (42.58 ± 0.49 U/ml). Furthermore, LEF-CS-NE reduced serum levels of glutamic pyruvic transaminase (GPT) to (83.19%) and glutamic oxaloacetic transaminase (GOT) to (40.68%) compared to the control + ve group. The effects of LEF-CS-NE were also superior to both pure and market LEF and showed better results in histopathological studies of paws, liver, kidney, lung, and heart. The remarkable therapeutic and safety profile of LEF-CS-NE makes it a potential oral system for the management of RA.

miRNAs orchestration of gallbladder cancer - Particular emphasis on diagnosis, progression and drug resistance.

Gallbladder cancer (GBC) is characterized by a highly invasive nature and a poor prognosis, with adenocarcinoma being the main histological subtype. According to statistical data, patients diagnosed with advanced GBC have a survival rate of less than 5% for 5 years. Despite the novel therapeutic techniques, the unsatisfactory results could be related to the underlying biology of tumor cells and resistance to chemotherapy. Early diagnosis is more important than clinical therapy as it assists in determining the pathological stage of cancer and facilitates the selection of appropriate medication. Hence, it is very important to understand the precise pathogenesis of GBC and to discover potential novel biomarkers for early diagnosis of GBC. Non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been found to influence the transcriptional regulation of target genes associated with cancer, either directly or indirectly. microRNAs are a group of small, non-coding, single-stranded RNAs that are expressed endogenously. miRNAs play significant roles in various fundamental cellular processes. Therefore, miRNAs have the potential to serve as valuable biomarkers and therapeutic targets for GBC.

Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation.

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3-4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of -27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62-77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.

Famotidine-loaded solid self-nanoemulsifying drug delivery system demonstrates exceptional efficiency in amelioration of peptic ulcer.

Famotidine (FMD) is a highly potent H2-receptor antagonist used in peptic ulcer treatment. However, the drug possesses poor aqueous solubility and permeability. FMD-loaded solid self-nanoemulsifying drug delivery system (FMD-S-SNEDDS) comprised of Labrafil® M 1944 CS, Tween® 20 and PEG 400, adsorbed on Aerosil® 200, has been developed. FMD-S-SNEDDS has demonstrated acceptable micromeritic properties, and upon reconstitution in water, spherical nanosized particles were released, as demonstrated by dynamic light scattering studies and transmission electron microscopy imaging. High encapsulation efficiency of FMD in the developed SNEDDS has been attained, and the saturated solubility of the drug has increased by 20-fold when it was incorporated in the SNEDDS. Several in vitro characterizations have been carried out, including, Fourier transform-infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and drug dissolution studies. In vivo, upon administration of the free drug suspension, marketed product (FAMOTIN®) and FMD-S-SNEDDS (40 mg/kg) in peptic ulcer rat models, FMD-S-SNEDDS and the marketed FMD demonstrated 12.5- and 4.7-fold reduction in ulcers number, and 28.7- and 7.2-fold reduction in ulcer severity, respectively, compared to the control untreated animals. FMD-S-SNEDDS showed a significant (p < 0.05) increase in the levels of depleted glutathione and endothelial nitric oxide synthase, and significantly (p < 0.05) reduced the elevated level of malondialdehyde, as compared to the free and marketed FMD. Only FMD-S-SNEDDS could restore the elevated proton pump activity and cyclic adenosine monophosphate RNA expression to their normal levels. Hence, FMD-S-SNEDDS provides a great potential as a nanotherapeutic system for treatment of peptic ulcer.

Antibiotic misuse and compliance with infection control measures during COVID-19 pandemic in community pharmacies in Egypt.

BACKGROUND: Globally, antibiotics misuse by the public has been reported in the era of COVID-19, despite the discouraging instructions of the World Health Organization, especially for mild cases. OBJECTIVE: Is to describe this antibiotic misuse and its contributing factors. Also, to measure the pharmacists' application of infection preventive practices during the pandemic. METHODS: A cross-sectional study was conducted among randomly selected Egyptian community pharmacists (Center, East, Delta, and Upper Egypt) using a questionnaire and direct interviews from 1 to 30 August 2020. The questionnaire consisted of two parts, the first covered pharmacist's demographic data and their application of basic infection preventive practices (eg, wearing face masks, regular hand sanitization, etc), and the other part was related to antibiotic dispensing patterns. Data were descriptively analyzed and the impact of participant experience on the responses was evaluated using the χ2 test. RESULTS: From 480 randomly selected Egyptian community pharmacists, 413 (87%) consented to participate in the study. 86.7% of the participants were keen to wear face masks (n = 358) and 86.2% kept regular hand sanitization (n = 356); whereas, 46.9% (n = 194) maintained adequate antibiotic stock supply during the pandemic. Nearly 67% (n = 275) of the pharmacists reported that patients were more likely to be given antibiotics for showing any sign or symptom of COVID-19 infection, and 82% (n = 74 278) of the dispensed antibiotics were given upon physician recommendation. Azithromycin, Ceftriaxone, and Linezolid were the major antibiotics dispensed to COVID-19 presumptive patients Azithromycin was given to ~40% of presumptive patients showing only mild or moderate symptoms for 5-10 days. Additionally, antibiotic combinations were given to 74% (n = 62 479) of home-isolated patients for a maximum of 2 weeks. CONCLUSIONS: Pharmacists applied suitable sanitation and infection control protocols. Meanwhile, antibiotics were dispensed heavily during this pandemic without proper clinical indication and for long durations supporting the idea of antibiotic misuse.