In vitro and in vivo characterization of Miconazole Nitrate loaded transethosomes for the treatment of Cutaneous Candidiasis.

This study aimed to fabricate Miconazole Nitrate transethosomes (MCZN TESs) embedded in chitosan-based gel for the topical treatment of Cutaneous Candidiasis. A thin film hydration method was employed to formulate MCZN TESs. The prepared MCZN TESs were optimized and analyzed for their physicochemical properties including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (%EE), Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), deformability, and Transmission electron microscopy (TEM). In vitro release, skin permeation and deposition, skin irritation, antifungal assay, and in vivo efficacy against infected rats were evaluated. The optimized MCZN TESs showed PS of 224.8 ± 5.1 nm, ZP 21.1 ± 1.10 mV, PDI 0.207 ± 0.009, and % EE 94.12 ± 0.101 % with sustained drug release profile. Moreover, MCZN TESs Gel exhibited desirable pH, spreadability, and viscosity. Notably, the penetration and deposition capabilities of MCZN TESs Gel showed a 4-fold enhancement compared to MCZN TESs. Importantly, in vitro antifungal assay elaborated MCZN TESs Gel anti-fungal activity was 2.38-fold more compared to MCZN Gel. In vivo, studies showed a 1.5 times reduction in the duration of treatment MCZN TESs Gel treated animal group. Therefore, studies demonstrated that MCZN TESs could be a suitable drug delivery system with higher penetration and good antifungal potential.

Design and Evaluation of Continentalic Acid Encapsulated Transfersomal Gel and Profiling of its Anti-arthritis Activity.

Rheumatoid arthritis restricts the physical ability of patients and increases the disease burden; therefore, research has always been focused on evaluating better therapeutic options. The present research aimed to design Continentalic acid (CA)-loaded transfersomes (CA-TF) embedded in Carbopol gel containing permeation enhancer (PE) for the treatment of rheumatoid arthritis. CA-TF was developed via a modified thin film hydration method and incorporated into Carbopol 934 gel containing Eucalyptus oil (EO) as PE. The fabricated CA-TF showed particle size of < 140 nm with spherical geometry, optimal encapsulation efficiency (EE), and sustained drug release pattern. CA-TF-gel along with PE (CA-TF-PE-gel) showed better ex vivo skin penetration than plain CA gel and CA-TF-gel without PE. In vivo evaluation supported improved therapeutic outcomes of CA-TF-PE-gel in terms of behavioral findings, arthritic index, and histological findings whereas biochemical assays and pro-inflammatory cytokines (TNF-α and IL-1ß) showed a significant decrease in their levels. Furthermore, immunohistochemistry assay for Nrf2 and HO-1 signaling pathways showed significant improvement in the expression of the Nrf2, and HO-1 proteins to depict improvement in arthritic condition in the animal model. CA-TF-PE-gel significantly delivered CA to the diseased target site via a topical route with promising therapeutic outcomes displayed in the CFA-induced arthritic model.

Enhanced cardioprotective activity of ferulic acid-loaded solid lipid nanoparticle in an animal model of myocardial injury.

Myocardial infarction results in an increased inflammatory and oxidative stress response in the heart, and reducing inflammation and oxidative stress after MI may offer protective effects to the heart. In the present study, we examined the cardioprotective effects of ferulic acid (FA) and ferulic acid nanostructured solid lipid nanoparticles (FA-SLNs) in an isoproterenol (ISO) induced MI model. Male Sprague Dawley rats were divided into five experimental groups to compare the effects of FA and FA-SLNs. The findings revealed that ISO led to extensive cardiomyopathy, characterized by increased infarction area, edema formation, pressure load, and energy deprivation. Additionally, ISO increased the levels of inflammatory markers (COX-2, NLRP3, and NF-кB) and apoptotic mediators such as p-JNK. However, treatment with FA and FA-SLNs mitigated the severity of the ISO-induced response, and elevated the levels of antioxidant enzymes while downregulating inflammatory pathways, along with upregulation of the mitochondrial bioenergetic factor PPAR-γ. Furthermore, virtual docking analysis of FA with various protein targets supported the in vivo results, confirming drug-protein interactions. Overall, the results demonstrated that FA-SLNs offer a promising strategy for protecting the heart from further injury following MI. This is attributed to the improved drug delivery and therapeutic outcomes compared to FA alone.

Transfersomes: a Revolutionary Nanosystem for Efficient Transdermal Drug Delivery.

Transdermal delivery system has gained significance in drug delivery owing to its advantages over the conventional delivery systems. However, the barriers of stratum corneum along with skin irritation are its major limitations. Various physical and chemical techniques have been employed to alleviate these impediments. Among all these, transfersomes have shown potential for overcoming the associated limitations and successfully delivering therapeutic agents into systemic circulation. These amphipathic vesicles are composed of phospholipids and edge activators. Along with providing elasticity, edge activator also affects the vesicular size and entrapment efficiency of transfersomes. The mechanism behind the enhanced permeation of transfersomes through the skin involves their deformability and osmotic gradient across the application site. Permeation enhancers can further enhance their permeability. Biocompatibility; capacity for carrying hydrophilic, lipophilic as well as high molecular weight therapeutics; deformability; lesser toxicity; enhanced permeability; and scalability along with potential for surface modification, active targeting, and controlled release render them ideal designs for efficient drug delivery. The current review provides a brief account of the discovery, advantages, composition, synthesis, comparison with other cutaneous nano-drug delivery systems, applications, and recent developments in this area.

Nanotechnology: from In Vivo Imaging System to Controlled Drug Delivery.

Science and technology have always been the vitals of human's struggle, utilized exclusively for the development of novel tools and products, ranging from micro- to nanosize. Nanotechnology has gained significant attention due to its extensive applications in biomedicine, particularly related to bio imaging and drug delivery. Various nanodevices and nanomaterials have been developed for the diagnosis and treatment of different diseases. Herein, we have described two primary aspects of the nanomedicine, i.e., in vivo imaging and drug delivery, highlighting the recent advancements and future explorations. Tremendous advancements in the nanotechnology tools for the imaging, particularly of the cancer cells, have recently been observed. Nanoparticles offer a suitable medium to carryout molecular level modifications including the site-specific imaging and targeting. Invention of radionuclides, quantum dots, magnetic nanoparticles, and carbon nanotubes and use of gold nanoparticles in biosensors have revolutionized the field of imaging, resulting in easy understanding of the pathophysiology of disease, improved ability to diagnose and enhanced therapeutic delivery. This high specificity and selectivity of the nanomedicine is important, and thus, the recent advancements in this field need to be understood for a better today and a more prosperous future.

Arteriovenous fistula construction in chronic haemodialysis patients: comparison of end-to-side and side-to-side techniques.

OBJECTIVE: To compare the techniques of end-to-side and side-to-side anastomosis in arteriovenous fistulae construction in terms of success rate and immediate postoperative complications. DESIGN: Comparative study. PLACE AND DURATION OF STUDY: Ayub Hospital Complex, Abbottabad, from October 1999 to December 2002 and Khyber Teaching Hospital, Peshawar, from January 2003 to December 2003. PATIENTS AND METHODS: One hundred and ninety patients with end stage renal disease (ESRD) were included in the study. Arteriovenous fistula was constructed in these patients by two techniques i.e. end-to-side and side-to-side anastomosis. The two methods were compared in terms of duration of surgery, immediate success rate and short-term complications. RESULTS: Among 190 patients, 118 (62%) were males and 72 (38%) females. The age ranged between 24 to 66 years with average age of 54 years. Side-to-side anastomosis was done in 120 (63%) patients while end-to-side in 70 (37%) patients. The average duration of surgery in side-to-side group was 50 minutes and in end-to-side group it was 75 minutes. Bleeding occurred in 4(5.7%) cases in end-to-side group and 2(1.7%) patients in side-to-side group requiring re-exploration. The immediate failure rate of the procedure was 2.5% in side-to-side group and 7.5% in end-to-side group. Wound infection occurred in 1(1.4%) case in end-to-side group and 2(1.7%) cases in side-to-side group. CONCLUSION: In patients with end stage renal disease (ESRD) arteriovenous fistula construction by side-to-side anastomosis is less time-consuming and has less complications as compared to end-to-side technique.