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Walaa Ebrahim Abd El Hady,1 Ghada Ahmed El-Emam,1 Nora E Saleh,2 Marwa M Hamouda,2 Amira Motawea1 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, EgyptCorrespondence: Amira Motawea, Email a_metawea@mans.edu.egBackground: Schistosomiasis is a chronic debilitating parasitic disease accompanied with severe mortality rates. Although praziquantel (PZQ) acts as the sole drug for the management of this disease, it has many limitations that restrict the use of this treatment approach. Repurposing of spironolactone (SPL) and nanomedicine represents a promising approach to improve anti-schistosomal therapy. We have developed SPL-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) to enhance the solubility, efficacy, and drug delivery and hence decrease the frequency of administration, which is of great clinical value.Methods: The physico-chemical assessment was performed starting with particle size analysis and confirmed using TEM, FT-IR, DSC, and XRD. The antischistosomal effect of the SPL-loaded PLGA NPs against Schistosoma mansoni (S. mansoni)-induced infection in mice was also estimated.Results: Our results manifested that the optimized prepared NPs had particle size of 238.00 ± 7.21 nm, and the zeta potential was − 19.66 ± 0.98 nm, effective encapsulation 90.43± 8.81%. Other physico-chemical features emphasized that nanoparticles were completely encapsulated inside the polymer matrix. The in vitro dissolution studies revealed that SPL-loaded PLGA NPs showed sustained biphasic release pattern and followed Korsmeyer–Peppas kinetics corresponding to Fickian diffusion (n< 0.45). The used regimen was efficient against S. mansoni infection and induced significant reduction in spleen, liver indices, and total worm count (ρ< 0.05). Besides, when targeting the adult stages, it induced decline in the hepatic egg load and the small intestinal egg load by 57.75% and 54.17%, respectively, when compared to the control group. SPL-loaded PLGA NPs caused extensive damage to adult worms on tegument and suckers, leading to the death of the parasites in less time, plus marked improvement in liver pathology.Conclusion: Collectively, these findings provided proof-of-evidence that the developed SPL-loaded PLGA NPs could be potentially used as a promising candidate for new antischistosomal drug development.Keywords: spironolactone, poly (lactic-co-glycolic acid), nanoparticles, Schistosoma mansoni, egg load, oogram

The practical application of genistein (GEN) as a drug system is hindered by its low aqueous solubility and poor oral bioavailability. Encapsulation of poor water-soluble drug was considered as one of the widely used approaches to overcome such of these obstacles. The primary goal of this research was to in situ encapsulate the hydrophobic GEN during the electrosynthesis of DNA nanospheres as a delivery system (Es GEN@DNA) with appropriate drug release properties. The prepared Es GEN@DNA nanospheres were characterized using UV-visible spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscope (TEM), zeta potential and stability test. The results revealed that GEN was successfully encapsulate in situ during the DNA electrospherization (Es GEN@DNA) as core shell like structure (Core: GEN and Shell: DNA) with a wonderful stability against time. Furthermore, the drug encapsulation % was studied. In addition, the drug release efficiency of Es GEN@DNA was recorded and theoretically visualized to understand the mechanism and kinetics of GEN drug release. %Encapsulation of GEN within DNA nanospheres was found to be 89.62%. Es GEN@DNA release profile explored that the well entrapped GEN within the DNA nanospheres could be a promising for sustained drug release. Besides, we overcome the dilemma of using a fractal or fractional kinetics model by introducing a general fractional kinetic equation that involves a time-dependent rate coefficient, which introduced that the solution of the fractional kinetic model is capable of fitting the release data profiles of free GEN and Es GEN@DNA.

The practical application of genistein (GEN) as a drug system is hindered by its low aqueous solubility and poor oral bioavailability. Encapsulation of poor water-soluble drug was considered as one of the widely used approaches to overcome such of these obstacles. The primary goal of this research was to in situ encapsulate the hydrophobic GEN during the electrosynthesis of DNA nanospheres as a delivery system (Es GEN@DNA) with appropriate drug release properties. The prepared Es GEN@DNA nanospheres were characterized using UV-visible spectroscopy, X-ray diffraction analysis (XRD), transmission electron microscope (TEM), zeta potential and stability test. The results revealed that GEN was successfully encapsulate in situ during the DNA electrospherization (Es GEN@DNA) as core shell like structure (Core: GEN and Shell: DNA) with a wonderful stability against time. Furthermore, the drug encapsulation % was studied. In addition, the drug release efficiency of Es GEN@DNA was recorded and theoretically visualized to understand the mechanism and kinetics of GEN drug release. %Encapsulation of GEN within DNA nanospheres was found to be 89.62%. Es GEN@DNA release profile explored that the well entrapped GEN within the DNA nanospheres could be a promising for sustained drug release. Besides, we overcome the dilemma of using a fractal or fractional kinetics model by introducing a general fractional kinetic equation that involves a time-dependent rate coefficient, which introduced that the solution of the fractional kinetic model is capable of fitting the release data profiles of free GEN and Es GEN@DNA.

The aim of the current study is to evaluate the remineralization potential of experimental tricalcium silicate (TCS) paste in comparison with more popular remineralizing agents like silver diamine fluoride potassium iodide (SDF-KI) and casein phosphopeptide amorphous calcium phosphate (CPP-ACP) on early enamel lesions.Forty-five patients in the age range of 15-50 years had early enamel lesions on the buccal surface of molar teeth. The patients were randomly divided into three treatment groups (SDF-KI, CPP-ACP, and TCS group) with 15 patients per group. Lesions were evaluated clinically by DIAGNOdent pen immediately and after 3,6,12, and 24 months of treatment.The study was completed with 45 patients and 92 teeth. Twice-daily application of CPP-ACP and TCS paste showed a significant remineralization effect on early enamel lesions after 24 months (p 0.001). Also, annual application of SDF-KI showed a significant remineralization effect after 24 months (p 0.001). There was a significant difference between (SDF-KI and CPP-ACP) and (SDF-KI and TCS) at the different follow-up periods 3,6,12, and 24 months (p 0.001). Meanwhile, there was no significant difference between CPP-ACP and TCS at the mentioned follow-up periods (p 0.05).TCS showed potential remineralization for early enamel lesions.Experimental TCS is a promising remineralizing agent for management of early enamel lesions.

Venlafaxine (VEN) is an antidepressant drug, but its delivery progress combined with a dependence on pathways and the incidence of toxicities that have infrequently led to FDA endorsement. This work focuses on developing novel electrospun polymeric nanofibers (NFs) for buccal delivery of VEN to avoid the hepatic metabolism, enzymatic degradation in the GIT, and develop an effective control of drug release. The optimized NFs were obtained by blending polylactic acid (PLA) and poly (ɛ-caprolactone) (PCL) and were characterized for morphology, drug-loading, FTIR, XRD, DSC, and in vitro drug release. Ex vivo permeability of the blend NFs was assessed using chicken pouch mucosa compared to VEN suspension followed by histopathological examination. Further, the cytotoxic effect was evaluated in three different cell lines using WST-1 assay. SEM morphologies refer to defect-free uniform NFs of PLA, PCL, and PLA/PCL mats. These fibers had a diameter ranging from 200–500 nm. The physico-thermal characterization of NFs depicted that the drug was successfully loaded and in an amorphous state in the PLA/PCL NFs. The cumulative release of NFs substantiated a bi-phasic profile with an initial burst release and a second sustained phase that reached 80% over 96 h following a non-Fickian diffusion mechanism. Ex vivo permeation emphasizes the major enhancement of the sustained drug release and the noticeable decrease in the permeability of the drug from NFs. Histopathology and cell toxicity studies demonstrated the preserved mucosal architecture and the preclinical safety. The developed PLA/PCL NFs can be promising drug carriers to introduce a step-change in improved psychiatric treatment healthcare.

Objective The aim of this study is to develop, and characterize nanostructured lipid carriers (NLCs) of phenytoin (PHT) in order to improve its entrapment efficiency and sustained release to improve the healing process. Methods Twenty-seven patients with neuropathic diabetic foot ulceration (DFU) were enrolled in this study. Patients were comparable regarding size, grading of ulcer and control of diabetes with no major deformity. All patients were managed by weekly sharp debridement if indicated and offloaded with cast shoes. They were equally divided into three groups: PHT-NLC-hydrogel (0.5%w/v), phenytoin hydrogel (0.5%w/v) and blank hydrogel groups. Changes in wound area were monitored over 2 months. Results Baseline wound area of PHT-NLC, PHT and blank hydrogels were 5.50 ± 3.66, 3.94 ± 1.86 and 5.36 ± 2.14 cm2, respectively. Ulcers treated with PHT-NLC hydrogel showed smaller wound area compared to control groups (ρ Conclusion PHT-NLC hydrogel speeds up the healing process of the DFU without adverse effects when compared to the positive and negative control hydrogels. Moreover, the study can open a window for topical application of NLCs loaded with PHT in the treatment of numerous dermatological disorders that resist conventional treatment. Key message The delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms. In this manuscript, the impact of topical phenytoin loaded nanostructured lipid carrier in improving wound healing in patients with neuropathic diabetic foot ulceration was investigated. Phenytoin loaded nanostructured lipid carrier dressing was found to be more effective than phenytoin hydrogel at the same concentration in healing of neuropathic diabetic foot ulcer.

Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities.Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied.Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (-14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated.Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2

We describe new method for preparing DNA nanospheres for a self-assembled atenolol@DNA (core/shell) drug delivery system. In this paper, we propose the electrochemical transformation of an alkaline polyelectrolyte solution of DNA into DNA nanospheres. We successfully electrosynthesized DNA nanospheres that were stable for at least 2 months at 4 °C. UV–visible spectra of the prepared nanospheres revealed a peak ranging from 372 to 392 nm depending on the DNA concentration and from 361 to 398.3 nm depending on the electrospherization time. This result, confirmed with size distribution curves worked out from transmission electron microscopy (TEM) images, showed that increasing electrospherization time (6, 12 and 24 h) induces an increase in the average size of DNA nanospheres (48, 65.5 and 117 nm, respectively). In addition, the average size of DNA nanospheres becomes larger (37.8, 48 and 76.5 nm) with increasing DNA concentration (0.05, 0.1 and 0.2 wt%, respectively). Also, the affinity of DNA chains for the surrounding solvent molecules changed from favorable to bad with concomitant extreme reduction in the zeta potential from −31 mV to −17 mV. Principally, the attractive and hydrophobic interactions tend to compact the DNA chain into a globule, as confirmed by Fourier transform infrared spectroscopy (FTIR) and TEM. To advance possible applications, we successfully electro self-assembled an atenolol@DNA drug delivery system. Our findings showed that electrospherization as a cost–benefit technique could be effectively employed for sustained drug release. This delivery system achieved a high entrapment efficiency of 68.03 ± 2.7% and a moderate drug-loading efficiency of 3.73%. The FTIR spectra verified the absence of any chemical interaction between the drug and the DNA during the electrospherization process. X-ray diffraction analysis indicated noteworthy lessening in atenolol crystallinity. The present findings could aid the effectiveness of electrospherized DNA for use in various other pharmaceutical and biomedical applications.

The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy.The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets.The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (FeldeneThe obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.