El problema de ruteo e inventario (IRP, por sus siglas en inglés) es una extensión del problema de ruteo de vehículos (VRP). El IRP incluye tanto decisiones de ruteo como de inventario (Cordeau et al.,2007). Las principales decisiones que se toman en este problema son: ¿qué clientes voy a visitar?, ¿cuánto producto voy a entregar? y ¿qué ruta voy a utilizar? (Campbell et al., 1998). Este problema tiene múltiples aplicaciones (Moin y Salhi,2007).

Este trabajo está enfocado en la distribución del oxígeno y su objetivo es desarrollar un modelo matemático difuso que cree rutas de distribución en un horizonte de tiempo finito. Aquí se asume que los clientes pertenecen al sector industria y sector salud. Este trabajo cuenta con dos características principales: 1) dar prioridad a los clientes del sector salud (dada una norma del gobierno mexicano que pide cierta calidad del oxígeno para el área médica) y 2) considerar incertidumbre en la demanda. La incertidumbre se aborda utilizando números difusos triangulares y con el fin de comparar números difusos, se utiliza el método del segundo índice de Yager.

Se analiza la influencia del porcentaje de clientes con prioridad (0, 0.25, 0.5 y 0.75) en instancias de 5, 10, 15 y 20 clientes. En todos los casos, las instancias se resolvieron a optimalidad, sin embargo, el tiempo de ejecución incrementa de manera exponencial, tomando un mayor tiempo cuando existe 0% de prioridad en clientes, y aquellas instancias con 50% de prioridad se resuelve a menor tiempo.

Objective: The purpose of the present investigation is to formulate and evaluation of cubosome loaded in situ gel for fungal keratitis.

Material and Method: The cubosomes were prepared by a top-down approach. Optimization of cubosome using box Behnken design. As formulation (independent) variables, lipid concentration (X1), poloxamer 407 concentration(X2), and homogenizer speed (X3) were used. The dependent variable was particle size (Y1), entrapment efficiency (Y2), and drug release(Y3) were investigated. 3-d surface plots and contour plots were drawn and optimized by feasibility and grid search. Identification of drug and drug-excipient compatibility study was carried out by DSC and FTIR. Particle size, PDI, and Zeta potential were analyzed by a zetatrac particle size analyzer. Entrapment efficiency, Invitro drug release study and SEM study were performed for characterization of nanoparticles. Viscosity, Gelation time and temperature, pH were performed for the characterization of nanoparticle-loaded in situ gel. An ocular irritancy study was performed on a rabbit.

Result and Discussion: Cubosome was prepared by top-down method and optimized by Box-Behnken design and results show that particle size was found to be in the range of 200 to 350 nm, the entrapment efficiency was found to be in the range of 70-90%and drug release was found to be more than 80%. After preparing cubosome, that are incorporated into thermosensitive in situ gel for that carbopol 934: poloxamer 188 in the ratio of 1:20 were selected. The gelation time was found to be 41±1 second and the gelation temperature was found to be 28 ± 0.70 ºc. The checkpoint batch was formulated using the given value having predicted particle size, entrapment efficiency, and drug release respectively 209.106nm, 84.5541%, and 84.3765%, and actual (experimental) value particle size, entrapment efficiency, and drug release respectively 207.88nm, 83.79%, and 82.94%. That shows less % relative error. From the image, the surface of cubosomes can be easily studied as to whether it has a cubic shape. The drug was 90.22 % diffused after 4 hrs. study of the Franz diffusion cell. In the ocular irritancy, study results indicate that the optimized in situ gelling system was non-irritant and well tolerated by the rabbit’s eyes.

Conclusion: In this study cubosome loaded in situ gel for fungal keratitis in the ocular route demonstrate that the ocular route is a promising approach and may improve the retention time of drug by the ocular route and reduce side effects related to other routes also improve patient compliance. This cubogel is an ocular dosage form to boost corneal permeability and bioavailability. The developed novel formulation is promising for the ocular delivery of a drug.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), responsible for generating COVID-19, has spread worldwide and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020, being responsible for various damages to public health, social life, and the economy of countries. Its high rates of infectivity and mortality have stimulated researchers and pharmaceutical companies to search for new therapies against this disease. The findings in recent years regarding the structure and biochemistry of SARS-CoV2 are remarkable. 3CLpro is a potential target as an anti-SARS agent as it plays a vital role in the viral life cycle. Another promising target is the transmembrane protease serine 2 (TMPRSS2). Recent studies point to TMPRSS2 as one of the main targets responsible for a viral entry related to the cleavage of the S protein. Similar to cathepsins, TMPRSS2 is also responsible for the cleavage of the spike protein SARS-CoV2, which binds to the ACE2 receptor. Also, TMPRSS2 is one of the targets that may represent new alternatives in treating SARS-CoV2. In addition, the multitarget approach has grown in recent years. The design and identification of drugs that act on multiple targets can be the next stage in drug discovery campaigns. Finally, here using a virtual screening protocol docking-based in a multitarget approach, the drugs Raloxifene, Saquinavir, AFP-168, and Valrubicin show a potential inhibition of 3CLpro and TMPRSS2 and can be evaluated in vitro assay to prove your potential

Rosmarinic acid is a phenolic compound that occurs naturally in many higher plants, particularly Lamiaceae. The name of this acid is based on the plant's name from which it was first isolated, Rosmarinus officinalis. Since rosmarinic acid has several biological activities, including antioxidant, antibacterial, hepatoprotective, and cardioprotective properties, it has been very useful for pharmaceutical, cosmetic, and food applications. This work, in the form of a patent analysis, presents the state by introducing what has been innovated and patented concerning rosmarinic acid. Furthermore, a detailed analysis of the patentability, using the "chemical compounds search" of the PATENTSCOPE database, has been provided regarding publication years, jurisdictions, and patent classifications.

Introduction. IKERDATA, S.L. is a "start-up" company founded by professors from the UPV / EHU, the IKERBASQUE Foundation and the University of A Coruña (UDC), with the support of ZITEK, the program to support entrepreneurship on the Bizkaia Campus, to put in value its results of Research and development in transfer actions that help to improve the quality of care of public services and the competitiveness of the productive sector in our environment or area of ​​influence. We are focused on Analysis Services, Consulting, Training, Association of Research Consortiums, Knowledge Diffusion, etc. We specialize in the application of advanced computing techniques and procedures, including Artificial Intelligence (AI), statistics, complex networks, bioinformatics, chemoinformatics, pharmacoinformatics,... for decision-making and optimization of resources in the field of health, the Pharmaceutical Industry (early discovery and repositioning of drugs or vaccine design); in the validation and discovery of Biomarkers, Nanobiotechnology, Biotechnology, the fuel industry and biomedical engineering. IKERDATA, S.L. team develop, validate, and commercialize predictive models whose functions have been specifically designed to meet the demand of each company or project and we design the necessary tools to facilitate their use. In any case, ensuring the adequate transfer of technology to the recipient of our products. IKERDATA, S.L. team have extensive experience in the application of techniques and procedures of advanced computing and Artificial Intelligence (AI) in fields such as chemoinformatics, eHealth or pharmacoinformatics.

Contact. IKERDATA S.L., VAT No.: B16731879, PIC No.: 885528036, ZITEK, UPVEHU, University Startup, Supported by Biscay Provincial Council, and Researchers of University of Basque Country (UPV/EHU), KERBASQUE Foundation, Greater Bilbao, Basque Country, and UDC University of Coruña, Spain. Linkedin: https://www.linkedin.com/company/ikerdata/

Services. Artificial Intelligence (AI), Scientific Consulting, Computing, Software Development, Consortium Partnering, Regulatory Affairs Counseling, Publication, and Training Services. Area of Expertise: Software Development and Computing (AI, ML, Cheminfo., Bioinfo., Complex Networks) Commisioned Research. Consulting on Regulatory Affairs (Patents, Copyright, GDPR Data Protection). We Can Also Arrange/Sub-Contracting Experimental Scientific Services (Organic Synthesis, HPLC, NMR, IR Spectroscopy, CryoEM Imaging, Pharmacological Assays... ) with Partner University Labs to Corroborate Computing Outcomes.

Know How. We Develop Our Own Scientific Computing Algorithms and Software Tools with Original Artificial Intelligence, Statistics, Complex Networks Analysis, Bioinformatics and Cheminformatics Algorithms. Products: We Can Offer Scientific Computing Services or Implement, Validate, and Transfer User-Friendly Software Packages Offering Solutions to Practical Problems Tailored to Client Necessities. Product Applications: Decision Making and Resources Optimization in Drug Discovery, Vaccine Development, Biomarkers Validation, Pharmaceutical Formulation, Catalyst Design, Synthetic Routes Optimization, Nanosystems Design, Materials Discovery, Synthesis Optimization, Biofuel Blending, Food, Nutraceuticals, and Cosmetics Production, Toxicity Prediction, and Eco-Toxicity , Risk Assesment, ...

Standards. European General Data Protection Regulation (GDPR), REACH (1907/2006), OECD QSAR (2004), Cosmetics (1223/2009), Pesticides (1107/2009), etc.

*Note: Mol2Net conference is associated to different MDPI journals special issues guest edited by Mol2Net Conference Committee members. This is an strategy to increase the online post-publication visibility of papers and conference, promote post-publication brainstorming discussion, and increase authors feedback. This association implies that our conference perform post-publication indexing of selected papers already published in MDPI journals with the consent of the issue editors. We publish free-of-cost these post-publication summaries. They include a shortened title, corresponding author info, and paper cover pdf file. The cover pdf file contains paper first page with all authors, abstract, full reference , and link to original papers.

Reference: This is a post-publication summary note for the paper published in the special issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering, Edited by: Dr. I.A. Neacsu and Dr. B.S. Vasile, Managing Editor: C. Zha, Visit the link to see original paper. Reference: Pharmaceutics 2022, 14(12),
2692; https://doi.org/10.3390/pharmaceutics14122692

Summary. Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize the combination of curcumin, as a neurogenesis agent, with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate their effects on PC12 cellsʹ neuronal branching morphogenesis in the absence of nerve growth factor. Therefore, the effects of each component alone and in combination form on the cytotoxicity, neurogenesis, and neural branching morphogenesis were evaluated using MTT assay, immunofluorescence staining, and inverted microscopy, respectively. Results confirmed the effectiveness of the biocompatible iron oxide nanoparticles (with a size of about 100 nm) in improving the percentage of neural branching (p < 0.01) in PC12 cells. In addition, the combination use of these nanoparticles with curcumin could enhance the effect of curcumin on neurogenesis (p < 0.01). These results suggest that SPIONs in combination with curcumin could act as an inducing factor on PC12 neurogenesis in the absence of nerve growth factor and could offer a novel therapeutic approach to the treatment of neurodegenerative diseases.

Pharmaceutics 2022, 14(12), 2692; https://doi.org/10.3390/pharmaceutics14122692

*Note: Mol2Net conference is associated to different MDPI journals special issues guest edited by Mol2Net Conference Committee members. This is an strategy to increase the online post-publication visibility of papers and conference, promote post-publication brainstorming discussion, and increase authors feedback. This association implies that our conference perform post-publication indexing of selected papers already published in MDPI journals with the consent of the issue editors. We publish free-of-cost these post-publication summaries. They include a shortened title, corresponding author info, and paper cover pdf file. The cover pdf file contains paper first page with all authors, abstract, full reference , and link to original papers.

Reference: This is a post-publication summary note for the paper published in the special issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering, Edited by: Dr. I.A. Neacsu and Dr. B.S. Vasile, Managing Editor: C. Zha, Visit the link to see original paper. Reference: Pharmaceutics 2022, 14(11),
2403; https://doi.org/10.3390/pharmaceutics14112403

Summary. Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in C_max (1.07-folds), AUC_0-t (4.70-folds), t_1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.

Pharmaceutics 2022, 14(11), 2403; https://doi.org/10.3390/pharmaceutics14112403

*Note: Mol2Net conference is associated to different MDPI journals special issues guest edited by Mol2Net Conference Committee members. This is an strategy to increase the online post-publication visibility of papers and conference, promote post-publication brainstorming discussion, and increase authors feedback. This association implies that our conference perform post-publication indexing of selected papers already published in MDPI journals with the consent of the issue editors. We publish free-of-cost these post-publication summaries. They include a shortened title, corresponding author info, and paper cover pdf file. The cover pdf file contains paper first page with all authors, abstract, full reference , and link to original papers.

Reference: This is a post-publication summary note for the paper published in the special issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering, Edited by: Dr. I.A. Neacsu and Dr. B.S. Vasile, Managing Editor: C. Zha, Visit the link to see original paper. Reference: Pharmaceutics 2022, 14(11), 2384; https://doi.org/10.3390/pharmaceutics14112384
Summary: Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of −19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH.

Pharmaceutics 2022, 14(11), 2384; https://doi.org/10.3390/pharmaceutics14112384

*Note: Mol2Net conference is associated to different MDPI journals special issues guest edited by Mol2Net Conference Committee members. This is an strategy to increase the online post-publication visibility of papers and conference, promote post-publication brainstorming discussion, and increase authors feedback. This association implies that our conference perform post-publication indexing of selected papers already published in MDPI journals with the consent of the issue editors. We publish free-of-cost these post-publication summaries. They include a shortened title, corresponding author info, and paper cover pdf file. The cover pdf file contains paper first page with all authors, abstract, full reference , and link to original papers.

Reference: This is a post-publication summary note for the paper published in the special issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering, Edited by: Dr. I.A. Neacsu and Dr. B.S. Vasile, Managing Editor: C. Zha, Visit the link to see original paper. Reference: Pharmaceutics 2022, 14(10), 2072; https://doi.org/10.3390/pharmaceutics14102072

Summary: Glioblastoma (GBM) is a primary brain tumor that carries a dismal prognosis, which is primarily attributed to tumor recurrence after surgery and resistance to chemotherapy. Since the tumor recurrence appears near the site of surgical resection, a concept of immediate and local application of chemotherapeutic after initial tumor removal could lead to improved treatment outcome. With the ultimate goal of developing a locally-applied, injectable drug delivery vehicle for GBM treatment, we created elastin-like polypeptide (ELP) hydrogels. The ELP hydrogels can be engineered to release anti-cancer drugs over an extended period. The purpose of this study was to evaluate the biomechanical properties of ELP hydrogels, to characterize their ability to release doxorubicin over time, and to investigate, in vitro, the anti-proliferative effect of Dox-laden ELP hydrogels on GBM. Here, we present microstructural differences, swelling ratio measurements, drug release characteristics, and in vitro effects of different ELP hydrogel compositions. We found that manipulation of the ELP–collagen ratio allows for tunable drug release, that the released drug is taken up by cells, and that incubation with a small volume of ELP-Dox hydrogel drastically reduced survival and proliferation of GBM cells in vitro. These results underscore the potential of ELP hydrogels as a local delivery strategy to improve prognosis for GBM patients after tumor resection.

*Note: Mol2Net conference is associated to different MDPI journals special issues guest edited by Mol2Net Conference Committee members. This is an strategy to increase the online post-publication visibility of papers and conference, promote post-publication brainstorming discussion, and increase authors feedback. This association implies that our conference perform post-publication indexing of selected papers already published in MDPI journals with the consent of the issue editors. We publish free-of-cost these post-publication summaries. They include a shortened title, corresponding author info, and paper cover pdf file. The cover pdf file contains paper first page with all authors, abstract, full reference , and link to original papers.

Reference: This is a post-publication summary note for the paper published in the special issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering, Edited by: Dr. I.A. Neacsu and Dr. B.S. Vasile, Managing Editor: C. Zha, Visit the link to see original paper. Reference: Pharmaceutics 2022, 14(9), 1971; https://doi.org/10.3390/pharmaceutics14091971

Summary: Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.