Engineering tanshinone-loaded, levan-biofunctionalized polycaprolactone nanofibers for treatment of skin cancer.

Skin cancer is a challenging condition of the highest prevalence rate among other types of cancer. Thus, advancement of local therapeutic approaches for skin cancer is highly needed. Recently, the use of phytotherapeutics, like tanshinone IIA (Tan), as anticancer agents has become promising. In this work, we engineered Tan-loaded polycaprolactone nanofibers, biofunctionalized with levan and egg-lecithin (Tan@Lev/EL/PCL-NF) for local skin cancer therapy. Novel Tan@Lev/EL/PCL-NF were prepared using w/o-emulsion electrospinning, employing a 23-factorial design. Composite NF exhibited nanofiber diameter (365.56 ± 46.25 nm), favorable surface-hydrophilicity and tensile strength. Tan@Lev/EL/PCL-NF could achieve favorably controlled-release (100% in 5 days) and Tan skin-deposition (50%). In vitro anticancer studies verified prominent cytotoxicity of Tan@Lev/EL/PCL-NF on squamous-cell-carcinoma cell-line (SCC), with optimum cytocompatibility on fibroblasts. Tan@Lev/EL/PCL-NF exerted high apoptotic activity with evident nuclear fragmentation, G2/M-mitosis cell-cycle-arrest and antimigratory efficacy. In vivo antitumor activity was established in mice, confirming pronounced inhibition of tumor-growth (224.25 ± 46.89%) and relative tumor weight (1.25 ± 0.18%) for Tan@Lev/EL/PCL-NF compared to other groups. Tan@Lev/EL/PCL-NF afforded tumor-biomarker inhibition, upregulation of caspase-3 and knockdown of BAX and MKi67. Efficient anticancer potential was further confirmed by histomorphometric analysis. Our findings highlight the promising anticancer functionality of composite Tan@Lev/EL/PCL-NF, as efficient local skin cancer phytotherapy.

Pentoxifylline/Valsartan co-delivery in liposomal gel alters the inflammatory HMGB-1/ TLR pathway and promotes faster healing in burn wounds: A promising repurposed approach.

Burn wounds are one of the most severe complex forms of trauma. Hence, new treatment strategies that facilitate the healing process; reduce the severity and the healing time is the main concern of the health care systems. In this work, pentoxifylline-valsartan, (PTX- VAL), loaded liposomes integrated into gel were designed for the first time as a novel co-delivery carrier for the treatment of burn wounds. The objective of this work was to investigate the ability of the nano-based liposomal system to co-entrap two repurposed drugs; hydrophilic pentoxifylline and lipophilic valsartan for topical treatment of burn wounds. The impact of increasing the phospholipid amount to enhance the co-entrapment of PTX and VAL was investigated and in-vitro evaluation of the prepared formulations was conducted to choose the optimum composition with the highest entrapment of both drugs adopting a simple, reliable derivative spectrophotometric method. Structure elucidation was also performed using a transmission electron microscope. In addition, A simple selected derivative spectrophotometric method was developed for the assay of PTX-VAL novel combination. The proven selectivity, precision and accuracy assured the reliability of this analytical method. Being economic and fast makes routine application of the developed analytical method is recommended in pharmaceutical industry. The selected liposomal formulation integrated into gel matrix (PTX-VAL-LG) showed; nanometric size, acceptable entrapment efficiency of both PTX and VAL as well as sustained release profiles and thus, enhanced action.

Cicatricial alopecia: do clinical, trichoscopic, and histopathological diagnosis agree?

INTRODUCTION: Cicatricial alopecia (CA) results from irreversible destruction and fibrosis of hair follicles. Trichoscopy offers a noninvasive method for diagnosis. METHODS: Thirty-two patients clinically diagnosed with CA were subjected to trichoscopy and histopathology assessment. The sensitivity and specificity of clinical and trichoscopic diagnoses were compared to histopathology. RESULTS: Thirty-two patients were clinically diagnosed as follows: 12 with discoid lupus erythematosus, four with lichen planopilaris (LPP), two with frontal fibrosing alopecia (FFA), three with folliculitis decalvans (FD), nine with central cicatricial centrifugal alopecia (CCCA), and two with long-term alopecia areata. Trichocopy revealed discoid lupus in 13 patients, LPP in nine, FFA in two, FD in three, central centrifugal alopecia in four, and pseudopelade in one. Histopathology confirmed discoid lupus in 13 patients, LPP in five, FFA in two, FD in three, CCCA in six, pseudopelade in two, and sarcoidosis in one. The sensitivity and specificity of clinical diagnosis were 69.2% and 84.2% in discoid lupus, 40.0% and 92.6% in LPP, 100.0% and 100.0% in FFA, 66.7% and 96.6% in FD, and 66.7% and 80.8% in central centrifugal alopecia. The sensitivity and specificity of trichoscopy were 84.6% and 89.5% in discoid lupus, 100.0% and 85.2% in LPP, 100.0% and 100.0% in FFA and FD, 66.7% and 100.0% in central centrifugal alopecia, and 50.0% and 100.0% in pseudopelade. CONCLUSIONS: Trichoscopy can be equivalent to histopathology for diagnosing some cases of CA.

Chitosan, magnetite, silicon dioxide, and graphene oxide nanocomposites: Synthesis, characterization, efficiency as cisplatin drug delivery, and DFT calculations.

Drug delivery systems with controlled release have been considered important tools for the treatment of various diseases. The efficacy of the drug can be enhanced by increasing its solubility, stability, bioavailability, and specific site delivery. Herein, we investigated cisplatin (cisP) loading efficacy and release potentiality on chitosan (CS) functionalized with magnetite (M), silicon dioxide (S), and graphene oxide (GO) nanoparticles. Different nanocomposites [chitosan-coated magnetite, silicon dioxide, and graphene oxide (CS/M/S/GO); chitosan-coated magnetite and silicon dioxide (CS/M/S); chitosan-coated silicon dioxide (CS/S); and chitosan-coated magnetite (CS/M)] were prepared. The prepared nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy, transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). DFT calculations were employed to explore the interaction mechanism of cisP with a selected chitosan-functionalized nanocomposite in the gas phase and water media. The UV-Vis spectroscopy was used to study cisP loading and release from the prepared nanocomposites. The results showed that the highest loading efficacy was achieved by CS/M and CS/M/S/GO nanocomposites (87% and 84% respectively). While the releasing potentiality for CS/M composite was the highest compared with the other ones (91%).

Enhancing Tumor Targeting Efficiency of Radiolabeled Uridine (via) Incorporation into Nanocubosomal Dispersions.

Background: Several nanosystems are currently being utilized to enhance the targeting efficiency of several cancer chemotherapeutic agents. This study was designed to improve tumor accumulation of iodine-125 (125I)-uridine via incorporation into a nanocubosomal preparation. Materials and Methods: Nanocubosomes were prepared with the aid of Glycerol mono-oleate and Pluronic F127. Each prepared nanocubosomal preparation was adequately characterized by testing their particle size, polydispersity index (PDI), ζ potential (ZP), and transmission electron microscopy. The radiolabeling of uridine with 125I was attempted using several oxidizing agents to achieve a high radiochemical yield, and the factors affecting the reaction yield were studied in detail. A comparative biodistribution study of free 125I-uridine and 125I-uridine loaded nanocubosomes was performed in normal and tumor bearing mice. The biodistribution was evaluated by intravenous injection of the sterile test solution, and animals were anesthetized and dissected at different time intervals postinjection (p.i.). Results: 125I-uridine was obtained in a high radiochemical yield (92.5% ± 0.8%). Afterward, 125I uridine was incorporated in a selected nanocubosome formulation, which showed nanosized cubic particles (178.6 ± 0.90 nm) with PDI (0.301 ± 0.04) and a ZP (34.35 ± 0.4). The biodistribution studies revealed that 125I-uridine nanocubosomes showed higher tumor localization (3.1 ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 6.2) compared with the free 125I-uridine (2.7% ± 0.4%IA/g at 2 h p.i. and a tumor/muscle ratio of 3.3). Conclusion: The results of this study confirmed that 125I-uridine loaded nanocubosome had better efficiency in targeting the tumor site, which makes it an adequate targeting agent for tumor imaging.

Comparative study on radiolabeling and biodistribution of core-shell silver/polymeric nanoparticles-based theranostics for tumor targeting.

A simple and rapid method for radiolabeling of three types of Ag NPs has been performed using 125I isotope, with high labeling yields, >90% without disturbing the optical properties. All the factors affecting labeling yield were studied. In order to monitor the in-vivo tissue uptake of radiolabeled Ag NPs using γ-rays, Ag-based radioiodo-NPs with a maximum labeling yield were intravenously injected in normal and solid tumor bearing mice. The preliminary biodistribution study revealed that this new radioiodo-NPs have a high affinity to be localized in the tumor site for a long period of time. The reported highly efficient method provides new radiolabeled Ag-based NPs as tumor-specific agents for both diagnostic and therapeutic applications.

Single Versus Double Ureteral Stent Placement After Laser Endoureterotomy for the Management of Benign Ureteral Strictures: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Endoureterotomy is a viable option for treating patients with benign ureteral stricture. We compared the efficacy and safety of double versus single ureteral stent placement after laser endoureterotomy. PATIENTS AND METHODS: This study included 55 patients with benign ureteral strictures; all patients underwent retrograde laser endoureterotomy. Patients were randomized either to single or double ureteral stents. Single stents were placed in 27 ureters while double stents were placed in 28 ureters. The stent diameter used was 7 F, and stents were indwelling for 8 weeks. Imaging was performed 1 month after stent removal and repeated regularly every 3 months. Clinical characteristics, operative results, and functional outcomes were compared for strictures managed in both groups. Success was evaluated both subjectively and objectively. RESULTS: Fifty-five patients with a mean age of 46 (16-75) years had benign ureteral strictures; the mean stricture length was 1.92 (1-3) cm. The mean follow-up was 25.7 (9-42) months. The overall success rate was 67.3% (37 patients) with no radiologic evidence of obstruction, 6 (10.9%) patients showed symptomatic improvement while 12 (21.8%) patients underwent surgical reconstruction. Success was significantly higher for ureteral strictures (>1.5 cm) managed with double stent placement (82.4%), compared with single stent placement (38.9%) with a P value of 0.009. CONCLUSIONS: Double stent placement of the ureter after laser endoureterotomy achieved a higher success rate compared with single stent placement in cases of benign ureteral strictures. Although ureteral strictures (≤1.5 cm) achieved better outcome after laser endoureterotomy, strictures (>1.5 cm) favored better with double stent versus single stent placement.

A specially tailored vancomycin continuous infusion regimen for renally impaired critically ill patients.

BACKGROUND: Vancomycin remains the gold standard for treatment of methicillin-resistant Staphylococcus aureus. Specially designed continuous infusion of vancomycin leads to better therapy. METHODOLOGY: A total of 40 critically ill patients who suffered from pneumonia susceptible to vancomycin, had serum creatinine >1.4 mg%, and oliguria <0.5 mL/kg/h for 6 h were included in the study with respiratory culture sensitivity to vancomycin ≤2 mg/L. Patients' clinical, microbiological, and biological data were obtained by retrospective analysis of the corresponding medical files before and after vancomycin treatment. Patients with serum creatinine level ≥4 mg% and patients who received renal replacement therapy during the treatment period were excluded. The patients were divided into two groups-group 1 (intermittent dosing) and group 2 (continuous infusion) based on the following formula: rate of vancomycin continuous infusion (g/day) = [0.0205 creatinine clearance (mL/min) + 3.47] × [target vancomycin concentration at steady state (µg/mL)] × (24/1000). Trough vancomycin serum levels were also assessed using high-performance liquid chromatographic technique. Patients' outcomes such as clinical improvement, adverse events, and 15-day mortality were reported. RESULTS: Group 2 showed significant reduction in blood urea nitrogen, creatinine serum levels, white blood cells, partial carbon dioxide pressure, body temperature, and Sequential Organ Failure Assessment score, while significant increase in partial oxygen pressure and saturated oxygen was also observed. A significantly shorter duration of treatment with a comparable vancomycin serum levels was also reported with group 2. CONCLUSION: After treatment, comparison in patients' criteria supports the superiority of using continuous infusion of vancomycin according to this equation in renally impaired patients.