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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.