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The global state of antibiotic resistance highlights the necessity for new drugs that can treat a wide range of microbial infections.

Noha M Badawi,1 Yasmeen M Attia,2 Dina M El-Kersh,3 Olfat A Hammam,4 Maha KA Khalifa5 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 2Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 3Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 4Department of Pathology, Theodor Bilharz Research Institute, Cairo, Egypt; 5Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, EgyptCorrespondence: Noha M Badawi, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, P.O. Box 11562, El Sherouk City, Cairo, Egypt, Email Noha.alaa@bue.edu.egPurpose: To design and optimize trans-cinnamic acid-loaded PLGA nanoparticles (CIN-PLGA-NPs) and assess its inhibitory effect on epithelial-mesenchymal transition (EMT) in triple-negative breast cancer.Methods: The quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the free trans-cinnamic acid (CIN-Free) was investigated in vitro using MDA-MB-231, triple-negative breast cancer cells, followed by scratch wound assay for evaluating the impact on the migratory potential of MDA-MB-231 cells. In vivo antitumor activity was evaluated using Ehrlich ascites carcinoma solid tumor animal model where tumor volumes were measured at different time points and necrotic/apoptotic indices were estimated in tumor sections. EMT markers, E- and N-cadherin, were assessed in solid tumors as well.Results: The optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of − 28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8± 1.89% of the total CIN-Free within 24 hours compared to 29± 1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition.Conclusion: Our findings proved the capability of PLGA nanoparticles in loading trans-cinnamic acid in addition to enhancing its antitumor efficacy in triple-negative breast cancer possibly via inhibiting EMT.Keywords: trans-cinnamic acid, epithelial-mesenchymal transition, PLGA nanoparticles, quality by design, breast cancer

To design and optimizeThe quality by design approach was used to correlate the formulation parameters (PLGA amount and Poloxamer188 concentration) and critical quality attributes (entrapment efficiency percent, particle size and zeta potential). Design of CIN-PLGA-NPs formulations was done based on central composite response surface design and formulated by nanoprecipitation method. In addition, the optimized CIN-PLGA-NPs formulation was further evaluated for morphology using transmission electron microscopy and in vitro dissolution test. The cytotoxicity of CIN-PLGA-NPs optimized formula in comparison to the freeThe optimized formulation showed entrapment efficiency of 76.98%, particle size of 186.3 nm with a smooth spherical surface and zeta potential of -28.47 mV indicating its stability. Furthermore, CIN-PLGA-NPs optimized formula released 60.8±1.89% of the total CIN-Free within 24 hours compared to 29±1.25% of the raw CIN-Free indicating improved dissolution rate. The optimized formula showed superior cytotoxicity on MDA-MB-231 cells compared to its free counterpart as well as increased wound closure percentage along with reduced tumor size in mice and increased necrotic and apoptotic indices. Tumor levels of E-cadherin and N-cadherin were indicative of EMT inhibition.Our findings proved the capability of PLGA nanoparticles in loading

Rofida Albash,1 Menna M Abdellatif,2 Mariam Hassan,3 Noha M Badawi4 1Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt; 2Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt; 3Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; 4Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Cairo, EgyptCorrespondence: Mariam HassanDepartment of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, EgyptTel +20(122)3376326Email mariam.hassan@pharma.cu.edu.egAim: To compare the ability of both terpesomes (TPs) and leciplex (LPs) loaded moxifloxacin hydrochloride (MOX) for enhancing ocular drug conveyance.Methods: Two separate 21 .31 full-factorial trials were established to determine the influence of multiple variables upon nanovesicles properties and select the optimized formulae using Design Expert® software. The thin-film hydration method was used to formulate TPs, while the single-step procedure was used for LPs. All formulae were characterized for their entrapment efficiency percent (EE%), particle size distribution (PS), polydispersity index (PDI), and zeta potential (ZP). Then, the optimized formulae were selected, evaluated, and compared for additional assessments.Results: The optimized formulae TP4 and LP1 showed EE% of 84.14± 0.21 and 78.47± 0.17%, PS of 578.65± 5.65 and 102.41± 3.39 nm, PDI of 0.56± 0.04 and 0.28± 0.01, ZP of − 12.50± 0.30 and 32.50± 0.50 mV, respectively. Further, LP1 showed enhanced corneal permeation across cow cornea compared to MOX solution and TP4. Besides, confocal laser scanning microscopy assessment viewed valuable infiltration from the fluoro-labeled LP through corneal layers compared to TP. LP1 showed spherical morphology and, its ability to adhere to mucus membranes was justified. Further, LP1 showed superiority over MOX solution in biofilm inhibition and eradication in addition to the treatment of infected mice with methicillin-resistant Staphylococcus aureus without any inflammatory response. Finally, the histopathological study verified the harmlessness and biocompatibility of the assembled LPs.Conclusion: The gained outcomes confirmed the capability of utilizing LPs as a successful nanovesicle for the ocular conveyance of MOX over TPs and MOX solution.Keywords: biofilm, confocal laser microscope, moxifloxacin hydrochloride, MRSA, leciplex, ocular drug conveyance, terpesomes

The purpose of this work was to incorporate an optimized pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) formula in a transdermal emulgel to evaluate its anticancer effect. The prepared emulgel formulae were evaluated for their physicochemical properties. An ex vivo permeation study was done through mouse skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of PE from SLNs transdermal emulgel through mouse skin followed non-Fickian diffusion transport. Further, in vivo study was done by applying the optimized PE-SLNs transdermal emulgel on mice skin bearing a solid form of Ehrlich ascites carcinoma (EAC) as well as free PE, control, placebo, and standard groups for comparison. In addition, histopathological examinations of the samples obtained from the EAC mice model were performed. The results proved that application of the selected PE-SLNs emulgel formulation on the mice skin bearing solid tumor revealed statistically significant anticancer effects.

The aim of this work was to study the influence of process variables on the quality attributes of pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) using Plackett–Burman design. PE-SLN formulations were prepared by hot homogenization followed by ultra-sonication technique and evaluated based on the dependent variables that were analyzed utilizing Statgraphics Centurion XV software. The lipid and surfactant (type and concentration), co-surfactant concentration, sonication time, and amplitude were selected as the independent variables (X1–X7). The dependent parameters were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative drug release (Y1–Y5). Response surface plots, Pareto charts, and mathematical equations were generated to study the influence of independent variables on the dependent quality parameters. Out of seven variables, X1, X2, and X6 have the main significant (p value < 0.05) effect on the entrapment efficiency, the cumulative drug release, the polydispersity index, respectively, while particle size was mainly affected by X3, X6 and zeta potential by X1, X3, and X4. Consequently, this screening study revealed that stearic acid as lipid, Tween 80 as surfactant, as well as sonication with short time and high amplitude can be selected for the development of PE-SLN formulation with minimum particle size, maximum zeta potential, highest entrapment, and sustained drug release behavior. Meanwhile, concentrations of lipid, surfactant, and co-surfactant are planned to be scaled up for further optimization study. In conclusion, the Plackett–Burman design verified its influence and significance in determining and understanding both process and formulation variables affecting the quality of PE-SLNs.

Noha M Badawi,1 Mahmoud H Teaima,2 Khalid M El-Say,3 Dalia A Attia,1 Mohamed A El-Nabarawi,2 Mohey MElmazar4 1Department of Pharmaceutics, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutics, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Pharmacology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt Background: Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer activity because of its polyphenols content. The main purpose of this study was to maximize the PE chemotherapeutic efficacy by loading it in an optimized solid lipid nanoparticles (SLNs) formula.Materials and methods: The influence of independent variables, which were lipid concentration (X1), surfactant concentration (X2) and cosurfactant concentration (X3), on dependent ones, which were particle size (Y1), polydispersity index (Y2), zeta potential (Y3), entrapment efficiency (Y4) and cumulative % drug release (Y5), were studied and optimized using the Box–Behnken design. Fifteen formulations of PE-SLNs were prepared using hot homogenization followed by ultra-sonication technique. Response surface plots, Pareto charts and mathematical equations were produced to study the impact of independent variables on the dependent quality parameters. The anti-proliferative activity of the optimized formula was then evaluated in three different cancer cell lines, namely, MCF-7, PC-3 and HepG-2, in addition to one normal cell line, HFB-4.Results: The results demonstrated that the particle sizes ranged from 407.5 to 651.9 nm and the entrapment efficiencies ranged from 56.02 to 65.23%. Interestingly, the 50% inhibitory concentration of the optimized formula had more than a 40-fold improved effect on the cell growth inhibition in comparison with its free counterpart. Furthermore, it was more selective against cancer cells than normal cells particularly in MCF-7 breast cancer cells.Conclusion: These data proved that nanoencapsulation of PE enhanced its anticancer efficacy. Therefore, our results suggested that a PE-loaded SLNs optimized-formula could be a promising chemo­therapeutic agent. Keywords: pomegranate extract, solid lipid nanoparticles, Box–Behnken design, optimization, cancer cell lines