Mohamad Mohey Aldin Elmazar

Purpose: The objective of the present study was to scrutinize the microsponges (MS) as a carrier system using Adapalene (ADA) as a model drug. Methods: Data modelling was implemented using Plackett-Burman design to identify the main variables affecting the formulation of ADA-MS. The adopted method of preparation for MS was quasi-emulsion solvent diffusion method. The nominated independent variables were volume of organic phase, sonication time, stirring speed, drug percent, polymer type, emulsifier concentration, and method of organic phase addition. As for the dependent variables, they included entrapment efficiency (E.E.%), production yield (P.Y.%), particle size (P.S.) and morphology. Furthermore, selected ADA loaded microsponges (ADA-MS) were in vitro assayed for their biological activities via cytotoxicity, UVA irradiation and cell viability, and antimicrobial activity. Results: The study indicated that the drug percent, polymer type and surfactant concentration have the key significant effect on E.E.% and P.Y.%, while, the drug percent, stirring speed and volume of organic phase have had a significant effect on P.S. and their morphology. Furthermore, ADA-MS had a momentous cytotoxic effect on A431 and M10 cell-lines with exceptional enrichment when the polymer Eudragit RS100 was used. Also, the ADA-MS increased the cell viability after UVA irradiation on HFB-4 cell-line by 14% to 43%, especially when using Ethyl Cellulose as a polymer. Lastly, the antimicrobial activity of ADA against Propionibacterium acnes was boosted when incorporated into MS. Conclusion: The Plackett−Burman design proved its impact in discerning preparation variables affecting the quality of ADA-MS formulation, with heightening of the in vitro biological activities of ADA. Thus, MS was presumed to be an auspicious carrier system for ADA. Graphical Abstract:

Extended infusion of piperacillin/tazobactam over 4 h has been proposed as an alternate mode of administration to the 30-min intermittent infusion to optimize treatment effects in patients with gram-negative bacterial infections. The study aimed to evaluate the extended infusion regimen of piperacillin/tazobactam in standings of efficacy, safety, and cost to the intermittent one in the treatment of gram-negative bacterial infections. A prospective randomized comparative study was performed on 53 patients, 27 in the intermittent infusion group and 26 in the extended infusion group. The primary outcome was the mean number of days to clinical success and the percentage of patients who were clinically cured after treatment. The secondary outcomes included mortality, readmission within 30-days, and cost-effectiveness analysis based on the mean number of days to clinical success. The clinical success rate was comparable in the two groups. Days on extended infusion were significantly lower than intermittent infusion (5.7 vs 8.9 days, respectively, p = 0.0001) as well as days to clinical success (4.6 vs 8.5 days, respectively, p = 0.026). The extended infusion was superior to the intermittent infusion regarding cost-effectiveness ratio ($1835.41 and $1914.09/expected success, respectively). The more cost-effective regimen was the extended infusion. Both regimens had comparable clinical and microbiological outcomes.

Background: 6-Mercaptopurine (6-MP) is a potential anti-cancer agent which its therapeutic and limitation applicability due to its high toxicity. Objective: Herein, 6-MP was loaded into tri-layered sandwich nanofibrous scaffold (the top layer composed of poly methyl methacrylate/polycaprolactone (PMMA/PCL), the middle layer was PCL/PMMA/6-MP, and the bottom layer was PCL/PMMA to improve its bioactivity, adjusting the release-sustainability and reduce its toxicity. Methods: Electrospun tri-layered nanofibers composed of PCL/PMMA were utilized as nano-mats for controlling sustained drug release. Four groups of sandwich scaffold configurations were investigated with alteration of (PMMA: PCL) composition. Results: The sandwich scaffold composed of 2%PCL/4%PMMA/1%6-MP showed the best miscibility, good homogeneity and produced the smoothest nanofibers and low crystallinity. All fabricated 6-MP-loaded-PCL/PMMA scaffolds exhibited antimicrobial properties on the bacterial and fungal organisms, where the cytotoxicity evaluation proved the safety of scaffolds on normal cells, even at high concentration. Scaffolds provided a sustained-drug release profile that was strongly dependent on (PCL: PMMA). As (PCL: PMMA) decreased, the sustained 6-MP release from PCL/PMMA scaffolds increased. Results established that ∼ 18% and 20% of 6-MP were released after 23h from (4%PCL/4%PMMA/1%6-MP) and (2%PCL/4%PMMA/1%6-MP), respectively, where this release was maintained for more than 20 days. The anti-cancer activity of all fabricated scaffolds was also investigated using different cancerous cell lines (e.g., Caco-2, MDA, and HepG-2) results showed that 6-MP-loaded-nanofibrous mats have an anti-cancer effect, with a high selective index for breast cancer. We observed that viability of a cancer cell was dropped to about 10%, using nanofibers containing 2%PCL/4%PMMA/1%6-MP. Conclusion: Overall, the PCL: PMMA ratio and sandwich configuration imparts a tight control on long-term release profile and initial burst of 6-MP for anticancer treatment purposes.

Objectives: Gemifloxacin Mesylate is a fourth generation fluoroquinolone antibacterial agent. A simple, accurate, and precise reversed phase (RP)ultra performance liquid chromatography (UPLC) method was developed and validated for short time analysis of Gemifloxacin Mesylate in its bulk and pharmaceutical preparation. Materials and Methods: The optimum separation was achieved at 0.5 +/- 0.03 min using an Acclaim(TM) RSLC 120 C18 column 2.2 mu m (2.1x100 mm) at 30 degrees C by isocratic mobile phase at pH 3.0 composed of acetonitrile:phosphate buffer (25 mM) in a ratio of 75:25 (v/v). The column effluents were monitored at 276 nm using a photodiode array detector at a flow rate of 0.5 mL/min. The method was validated according to International Conference on Harmonization guidelines. Results: The linearity of the calibration curve ranged from 0.5 mu g/mL to 10 mu g/mL and the square of the regression coefficient (r(2)) was 0.9991. The % relative standard deviation (RSD) of inter-day precision ranged from 0.081% to 1.233%, while for intra-day it ranged from 0.364% to 1.018%. The method was accurate with % recovery ranging from 93.71% to 100.29% and % RSD ranging from 1.054 to 2.722. The limit of detection and the limit of quantification were 0.066 and 0.2 pg/mL, respectively. Conclusion: The validated method proved its ability for the assay of Gemifloxacin Mesylate in its bulk and dosage form in a short time (less than 1 min). To the best of our knowledge, this is the first RP-UPLC method for the determination of Gemifloxacin Mesylate.

Oromuco-adhesive films for buccal delivery of Propolis extract (PPE) entrapped in niosomes, were prepared to treat oral recurrent aphthous ulcer (RAU). PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and in vitro release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7 ± 0.15 µg quercetin equivalents and phenolic content of 180.8 ± 0.11 µg gallic acid equivalents/mg. Multilamellar niosomes of 176–333 nm displayed entrapment efficiency of 91 ± 0.48%, PDI of 0.676 and zeta potential of −4.99. In vitro release after 8 h from niosomal dispersion and films were 64.05% and 29.09 ± 0.13% respectively. Clinical results revealed duration of film adherence from 2–4 h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4–5 h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.

Colorectal cancer (CRC) is the third most common cancer mortality worldwide. Although, 5-Fluorouracil (5-FU)-based chemotherapeutic regimens remain the mainstay for treatment of CRC, intrinsic and acquired resistance to 5-FU is the main reason for treatment failure and relapse. Adjunct or add-on therapy, therefore, should be thought of to enhance responsiveness to 5-FU. Verbascoside (VER) is a phenylethanoid glycoside ingredient present in many Plantago species and was widely used in traditional medicine. VER showed antiproliferative effects in many cancer types including CRC. In the present study, VER in Plantago seeds was identified using UPLC-MS/MS and quantified using newly developed and validated UPLC-DAD followed by investigating its potential sensitization of CRC cells to 5-FU in vitro. The potential impact on PI3K/AKT pathway was also investigated. A synergistic cytotoxic interaction between 5-FU and VER besides G1 cell cycle arrest were detected. Enhanced apoptosis mainly by affecting Bax and Bcl-2 and to a lesser extent Bcl-xL and p53 was also observed. Additionally, 5-FU combined to VER was capable of significantly reducing PI3K and p-AKT/total AKT ratio. Overall, these results suggest a potential role of VER as an adjuvant treatment to decrease the resistance of CRC cells to 5-FU possibly by targeting the PI3K/AKT pathway.

Thermoresponsive gels containing gold nanoparticles (AuNPs) were prepared using Pluronic®127 alone (F1) and with hydroxypropyl methylcellulose (F2) at ratios of 15% w/w and 15:1% w/w, respectively. AuNPs were evaluated for particle size, zeta-potential, polydispersity index (PDI), morphology and XRD pattern. AuNP-containing thermoresponsive gels were investigated for their gelation temperature, gel strength, bio-adhesive force, viscosity, drug content, in vitro release and ex-vivo permeation, in addition to in vitro antibacterial activity against bacteria found in burn infections, Staphylococcus aureus. In vivo burn healing and antibacterial activities were also investigated and compared with those of a commercial product using burn-induced infected wounds in mice. Spherical AuNPs sized 28.9–37.65 nm displayed a surface plasmon resonance band at 522 nm, a PDI of 0.461, and a zeta potential of 34.8 mV with a negative surface charge. F1 and F2 showed gelation temperatures of 37.2 °C and 32.3 °C, bio-adhesive forces of 2.45 ± 0.52 and 4.76 ± 0.84 dyne/cm², viscosities of 10,165 ± 1.54 and 14,213 ± 2.31 cP, and gel strengths between 7.4 and 10.3 sec, respectively. The in vitro release values of F1 and F2 were 100% and 98.03% after 6 h, with permeation flux values of (J₁) 0.2974 ± 2.85 and (J₂) 0.2649 ± 1.43 (µg/cm²·h), respectively. The formulations showed antibacterial activity with the highest values for wound healing properties, as shown in vivo and by histopathological studies. This study demonstrates that a smart AuNPs thermoresponsive gel was successful as an antibacterial and wound healing transdermal drug delivery system.