Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia

Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 °C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 °C; 60 h). The results showed that at 4 °C the viability was maintained above 80% for 48 h, at 8 °C decreased slightly, whereas at room temperature and 37 °C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1 × 106 cells/mL, which must be stored at 4 °C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h. © 2013 Elsevier B.V. All rights reserved.This study was supported by Grants RD08/0010/2005 (Red TERCEL) and PI10/00964 from Institute of Heath Carlos III and TRA-120 (Ministry of Health) to BS.Peer Reviewe

New nanotechnologies for the treatment and repair of skin burns infections

Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections.The authors would like to thank the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020, co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Some reasons which could induce to the students to choose an academic subject

El motivo de elección de una determinada asignatura por parte de los alumnos, ha sido frecuentemente interpretado bajo diferentes puntos de vista. En esta comunicación nuestro objetivo ha sido analizar los motivos de elección en distintos tipos de asignaturas con características peculiares cada una de ellas, concretamente dos de ellas son de libre configuración, siendo una de impartición en el campus andaluz virtual –Fotoprotección- y la otra en el campus virtual de la Universidad de Granada –Aplicación de la Tecnología Farmacéutica en el tratamiento del cáncer y del dolor-. La tercera asignatura seleccionada es una optativa -Farmacia Práctica- que se imparte actualmente en la Licenciatura en Farmacia. Se ha realizado un análisis de los diferentes motivos que impulsan a un alumno a la elección de una disciplina frente a otra, para ello se ha utilizado una de las herramientas de mayor uso, la encuesta anónima a todos aquellos que estaban matriculados. Las conclusiones de este estudio son diversas pero ante todo cabe señalar en el caso de las virtuales la facilidad de acceso y realización de las asignaturas virtuales, y destacar también que un título atractivo es fundamental en su elección. En el caso de la optativa el motivo fundamental ha sido aprender algo nuevo relacionado con su licenciatura y seguido muy de cerca por la facilidad de horario. Por tanto como conclusión definitiva es interesante destacar que tanto en un caso como en otro el alumno desea aprender algo atractivo y que se acomode fácilmente a su horario de estudio.The reason why a specific subject is chosen by the students has been frequently interpreted from several points of view. The aim of this study is to analyze the reasons why different types of subjects with particular characteristics are chosen. Specifically, two of these subjects are free electives: one of them –Fotoprotección- is imparted through the Andalusian Virtual Campus, and the other one –Aplicación de la Tecnología Farmacéutica en el tratamiento del cáncer y del dolorthrough the virtual campus of the University of Granada. The third subject chosen is optional - Farmacia Práctica- and it is at present imparted within the Degree in Pharmacy. The different reasons why a student chooses one subject against other have been analyzed using one of the most used tools: an anonymous survey to all the students enrolled. The conclusions of this study are diverse, but it is mainly to be remarked in the case of the virtual subjects their accessibility and easy implementation as well as the importance of an attractive title for the selection of a subject. The main reason in the case of the optional subject is to learn something new in relation to their Degree, followed very closely by its timetable. Therefore, as final conclusion, it is interesting to remark that the students want in both cases to learn something attractive that can be easily adapted to their study schedule

Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design, release profile and cytotoxicity in human Colon adenocarcinoma cell line

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 22 factorial design. The optimized formulation was composed of 10wt% of glyceryl behenate and 2.5wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1±0.114nm, with a polydispersity index (PI) of 0.171±0051 and zeta potential nearly neutral (3.10±0.166mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25°C for a period of 15days, whereas at 4°C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100g/mL) up to 48hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1±36.63nm (PI 0.491±0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.This work was financed through the projects M-ERA-NET/0004/2015-PAIRED, receiving financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. This work was also supported by the Spanish Ministry of Science and Innovation (MAT 2014-59134-R projects; 2014SGR-1023).info:eu-repo/semantics/publishedVersio

Clotrimazole multiple W/O/W emulsion as anticandidal agent: Characterization and evaluation on skin and mucosae

Clotrimazole (CLT) was formulated in a multiple W/O/W emulsion (ME) with the aim of evaluating its potential as topical anticandidal agent and comparing with marketed products. A previously evaluated CLT-ME was selected and physicochemically characterized. The in vitro release behavior and the ex vivo permeation profiles were assessed using Franz diffusion cells using three different types of biological membranes: human skin and porcine buccal, sublingual and vaginal mucosae. The antifungal activity against Candida strains was also tested. Results showed CLT-MEs sizes of 29.206 and 47.678??m with skin compatible pH values of 6.47 and 6.42 exhibiting high zeta potential values of -55.13 and -55.59?mV with dependence on the pH variation. The physicochemical stability was kept for a period of 180 days of storage at room temperature. CLT-MEs exhibited pseudoplastic behavior with hysteresis areas and viscosities of 286 and 331 mPa?s showing higher spreadability properties than commercial counterparts. An improved CLT release pattern was supplied by the ME system following a hyperbolic model. Likewise, ME system gave higher skin permeation flux of CLT than commercial reference. CLT amounts retained in the skin and mucosae were also higher than commercial references, which coupled with the higher antimycotic efficacy make CLT-MEs a great tool for clinical investigation of topical candidiasis treatments.Supplementary material related to this article can be found, in the online version, at doi: https://doi.org/10.1016/j.colsurfb.2018.11.070.info:eu-repo/semantics/publishedVersio

Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches

Cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) show clinical spectra that can range from a localized lesion (with a spontaneous healing process) to cases that progress to a generalized systemic disease with a risk of death. The treatment of leishmaniasis is complex since most of the available drugs show high toxicity. The development of an effective topical drug formulation for CL and ML treatment offers advantages as it will improve patient’s compliance to the therapy given the possibility for self-administration, as well as overcoming the first pass metabolism and the high costs of currently available alternatives. The most common dosage forms include solid formulations, such as membranes and semi-solid formulations (e.g., ointments, creams, gels, and pastes). Topical treatment has been used as a new route of administration for conventional drugs against leishmaniasis and its combinations, as well as to exploit new substances. In this review, we discuss the advantages and limitations of using topical drug delivery for the treatment of these two forms of leishmaniasis and the relevance of combining this approach with other pharmaceutical dosage forms. Emphasis will also be given to the use of nanomaterials for site-specific delivery

Developing Transdermal Applications of Ketorolac Tromethamine Entrapped in Stimuli Sensitive Block Copolymer Hydrogels

Purpose: In order to obtain dermal vehicles of ketorolac tromethamine (KT) for the local treatment of inflammation and restrict undesirable side effects of systemic levels hydrogels (HGs) of poloxamer and carbomer were developed. Methods: KT poloxamer based HG (KT-P407-HG) and KT carbomer based HG (KT-C940-HG) were elaborated and characterized in terms of swelling, degradation, porosity, rheology, stability, in vitro release, ex vivo permeation and distribution skin layers. Finally, in vivo anti-inflammatory efficacy and skin tolerance were also assessed. Results: HGs were transparent and kept stable after 3 months exhibiting biocompatible near neutral pH values. Rheological patterns fitted to Herschel-Bulkley for KT-C940-HG and Newton for KT-P407-HG due to its low viscosity at 25°C. Rapid release profiles were observed through first order kinetics. Following the surface the highest concentration of KT from C940-HG was found in the epidermis and the stratum corneum for P407-HG. Relevant anti-inflammatory efficacy of KT-P407-HG revealed enough ability to provide sufficient bioavailability KT to reach easily the site of action. The application of developed formulations in volunteers did not induce any visual skin irritation. Conclusions: KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect