Editorial for Special Issue 'Engineering and Characterisation of Novel Nanomedicine Formulations'.

Nanomedicine is the application of nanotechnology to achieve innovations in healthcare and involves the engineering of systems at the nanoscale (particle size < 1000 nm) with the aim of improving drug delivery [...].

Polycaprolactone microparticles for the subcutaneous administration of cannabidiol: in vitro and in vivo release.

Cannabidiol (CBD) has become a highly attractive entity in therapeutics. However, its low aqueous solubility, instability and handling problems limit the development of effective CBD formulations. Subcutaneously administered CBD-loaded polycaprolactone microparticles (MP) represent an interesting strategy to overcome these challenges. This work focuses on evaluating the pharmacokinetics of CBD formulated in polymer microparticles for subcutaneous administration and characterising its release. The mean release time (MRLT) parameter is used to compare the release of CBD from two microparticle formulations in vitro and in a mouse model. After the administration of CBD in solution, a bicompartmental distribution is observed due to the extensive diffusion to the brain, being the brain/blood AUC ratio 1.29. The blood and brain mean residence time (MRT) are 0.507 ± 0.04 and 0.257 ± 0.0004 days, respectively. MP prepared with two drug/polymer ratios (15/150-MP and 30/150-MP) are designed, showing similar in vitro dissolution profiles (similarity factor (f2) is 63.21), without statistically significant differences between MRLTin vitro values (4.68 ± 0.63 and 4.32 ± 0.05 days). However, considerable differences in blood and brain profiles between both formulations are detected. The blood and brain MRT values of 15/150-MP are 6.44 ± 0.3 days and 6.15 ± 0.25 days, respectively, whereas significantly lower values 3.91 ± 0.29 days and 2.24 ± 0.64 days are obtained with 30/150-MP. The extended release of CBD during 10 days after a single subcutaneous administration is achieved.

Quimioterapia nanométrica a base de cannabinoides para el tratamiento de tumores ginecológicos / Cannabinoid based chemo-nanotherapy for the treatment of gynecological malignancies

El cannabidiol está despertando un creciente interés como agente antitumoral. Sin embargo, no se ha estudiado su efecto en cáncer de ovario, uno de los tumores más agresivos en mujeres. En el presente trabajo se ha evaluado, por primera vez, el potencial uso del cannabidiol en solución y encapsulado en nanopartículas funcionalizadas con ácido fólico en cáncer de ovario, ya que estos tumores sobreexpresan los receptores de ácido fólico, permitiendo una acumulación selectiva de estas nanoformulaciones en las células tumorales. El cannabidiol en solución inhibe la proliferación y migración de las células SKOV-3. En terapia de combinación, aumenta significativamente la eficacia antitumoral del paclitaxel, presentando un efecto sensibilizador y sinérgico. En los modelos in ovo, la administración previa de cannabidiol en solución seguido de su coadministración con paclitaxel muestra un efecto inhibitorio sobre el crecimiento tumoral significativamente superior al paclitaxel en monoterapia. Las nanopartículas desarrolladas son eficazmente internalizadas por las células SKOV-3, presentando las nanopartículas con ácido fólico una captación más rápida. Aunque en los estudios de eficacia antitumoral in vitro las nanopartículas funcionalizadas no presentan una actividad antiproliferativa superior al cannabidiol en solución o a las nanopartículas no funcionalizadas, en los modelos in ovo su eficacia antitumoral es significativamente superior, indicando que el desarrollo de nanopartículas funcionalizadas con ácido fólico es una buena estrategia para vectorizar el cannabidiol a tumores de ovario. Por último, las nanopartículas de cannabidiol potencian el efecto antitumoral del paclitaxel, presentando las formulaciones funcionalizadas con ácido fólico una mayor eficacia que el cannabidiol en solución. (AU)

Cannabidiol has become in a potential anticancer agent. Nevertheless, it has not been evaluated in ovarian cancer, one of the most aggressive tumors in women. In this work, the potential use of cannabidiol in solution and encapsulated into polymeric nanoparticles coated with folic acid was evaluated for the first time for the treatment of ovarian cancer. Ovarian tumors over-express folic acid receptors and folic-acid-coated nanoformulations trend to be selectively accumulated at tumor site. Cannabidiol in solution administered as monotherapy inhibits the proliferation and migration of SKOV-3 cells. In combination therapy, it significantly increases the antitumor efficacy of paclitaxel, showing a sensitizer and synergistic effect. In ovo, the previous administration of cannabidiol in solution followed by its co-administration with paclitaxel, shows a significantly higher inhibitory effect on ovarian tumor growth than single paclitaxel. The developed nanoparticles are efficiently uptaken by SKOV-3 cells, showing folic acid coated formulations a faster internalization. Although coated formulations do not exhibit a higher in vitro antiproliferative effect compared to cannabidiol in solution or non-coated formulations, in ovo its antitumoral efficacy is significantly higher. This indicates thatfolic acid-coated nanoparticles represent a good strategy to target cannabidiol to ovarian tumors. Finally, cannabidiol-loaded nanoparticles improve the in vitro antiproliferative effect of paclitaxel, showing folic acid-coated-formulations a better efficacy than cannabidiol in solution. (AU)

Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with its incidence constantly increasing. To date, there is no cure for the disease, with a need for new and effective treatments. Morin hydrate (MH) is a naturally occurring flavonoid of the Moraceae family with antioxidant and anti-inflammatory properties; however, the blood-brain barrier (BBB) prevents this flavonoid from reaching the CNS when aiming to potentially treat AD. Seeking to use the LAT-1 transporter present in the BBB, a nanoparticle (NPs) formulation loaded with MH and functionalized with phenylalanine-phenylalanine dipeptide was developed (NPphe-MH) and compared to non-functionalized NPs (NP-MH). In addition, two formulations were prepared using rhodamine B (Rh-B) as a fluorescent dye (NPphe-Rh and NP-Rh) to study their biodistribution and ability to cross the BBB. Functionalization of PLGA NPs resulted in high encapsulation efficiencies for both MH and Rh-B. Studies conducted in Wistar rats showed that the presence of phenylalanine dipeptide in the NPs modified their biodistribution profiles, making them more attractive for both liver and lungs, whereas non-functionalized NPs were predominantly distributed to the spleen. Formulation NPphe-Rh remained in the brain for at least 2 h after administration.

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic.

Breast cancer is one of the most frequently diagnosed tumors and the second leading cause of cancer death in women worldwide. The use of nanosystems specifically targeted to tumor cells (active targeting) can be an excellent therapeutic tool to improve and optimize current chemotherapy for this type of neoplasm, since they make it possible to reduce the toxicity and, in some cases, increase the efficacy of antineoplastic drugs. Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla®, Enhertu®, Trodelvy®, and Abraxane®). Most of these nanomedicines are antibody-drug conjugates. In the case of HER-2-positive breast cancer, these conjugates (Kadcyla®, Enhertu®, Trastuzumab-duocarmycin, RC48, and HT19-MMAF) target HER-2 receptors, and incorporate maytansinoid, deruxtecan, duocarmicyn, or auristatins as antineoplastics. In TNBC these conjugates (Trodelvy®, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody-drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane® and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work, all these active targeted nanomedicines are discussed, analyzing their advantages and disadvantages over conventional chemotherapy as well as the challenges involved in their lab to clinical translation. In addition, examples of formulations developed and evaluated at the preclinical level are also discussed.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

PURPOSE: Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. METHODS: An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. RESULTS: The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. CONCLUSION: The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

The Chick Embryo Chorioallantoic Membrane Model: A Research Approach for Ex Vivo and In Vivo Experiments.

BACKGROUND: The chick chorioallantoic membrane (CAM) model has attracted a great deal of interest in pharmaceutical and biological research as an alternative or complimentary in vivo assay to animal models. Traditionally, CAM assay has been widely used to perform some toxicological studies, specifically to evaluate the skin, ocular and embryo toxicity of new drugs and formulations, and to perform angiogenesis studies. Due to the possibility to generate the tumors onto the CAM, this model has also become an excellent strategy to evaluate the metastatic potential of different tumours and to test the efficacy of novel anticancer therapies in vivo. Moreover, in the recent years, its use has considerably grown in other research areas, including the evaluation of new anti-infective agents, the development of biodistribution studies and in tissue engineering research. OBJECTIVE: This manuscript provides a critical overview of the use of CAM model in pharmaceutical and biological research, especially to test the toxicity of new drugs and formulations and the biodistribution and the efficacy of novel anticancer and antiinfective therapies, analyzing its advantages and disadvantages in comparison to animal models. CONCLUSION: The chick chorioallantoic membrane model shows a great utility in several research areas, such as cancer, toxicology, biodistribution studies and anti-infective therapies. In fact, it has become an intermediate stage between in vitro experiments and animal studies, and, in the case of toxicological studies (skin and ocular toxicity), it has even replaced the animal models.

Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives.

In the last decade, antibody-drug conjugates (ADCs), normally formed by a humanized antibody and a small drug via a chemical cleavable or non-cleavable linker, have emerged as a potential treatment strategy in cancer disease. They allow to get a selective delivery of the chemotherapeutic agents at the tumor level, and, consequently, to improve the antitumor efficacy and, especially to decrease chemotherapy-related toxicity. Currently, nine antibody-drug conjugate-based formulations have been already approved and more than 80 are under clinical trials for the treatment of several tumors, especially breast cancer, lymphomas, and multiple myeloma. To date, no ADCs have been approved for the treatment of gynecological formulations, but many formulations have been developed and have reached the clinical stage, especially for the treatment of ovarian cancer, an aggressive disease with a low five-year survival rate. This manuscript analyzes the ADCs formulations that are under clinical research in the treatment of gynecological carcinomas, specifically ovarian, endometrial, and cervical tumors.

Matrix tablets based on a novel poly (magnesium acrylate) hydrogel for the treatment of inflammatory bowel diseases.

The objective of this work was to evaluate the potential use of a new polymer (PAMgA) in the development sustained release matrix tablets for the treatment of bowel inflammatory diseases. For this purpose, budesonide, a highly lipophilic compound, was used as model drug. Tablets with two reticulation grades of PAMgA (PAMgA 5 and 40) and with 9 mg of budesonide were developed and characterized. All the studies were carried out using biorelevant media (FaSSGF and FaSSIF). Swelling and erosion of PAMgA tablets was influenced by the reticulation grade of the polymer and the biorelevant media assayed, being water uptake higher for PAMgA 40 tablets in intestinal fluid, whereas PAMgA 5 showed more intense erosion in this biorelevant medium. Budesonide was released slowly from PAMgA tablets, both in gastric and intestinal environment, following Super case II transport kinetics (relaxation-controlled delivery), with a lag time of around 1-2 h. When the dissolution medium was changed sequentially throughout the trial, 75% of the budesonide dose was released in a sustained manner between 4 and 20 h of testing from PAMgA tablets, showing a more controlled budesonide release than Entocort® and Budenofalk® (commercially available sustained release formulations of budesonide). In conclusion, PAMgA polymer allows controlling the release of highly lipophilic drugs as budesonide, being an useful excipient for the development of sustained release matrix tablets.

Active Targeted Nanoformulations via Folate Receptors: State of the Art and Future Perspectives.

In normal tissues, the expression of folate receptors is low and limited to cells that are important for embryonic development or for folate reabsorption. However, in several pathological conditions some cells, such as cancer cells and activated macrophages, overexpress folate receptors (FRs). This overexpression makes them a potential therapeutic target in the treatment of cancer and inflammatory diseases to obtain a selective delivery of drugs at altered cells level, and thus to improve the therapeutic efficacy and decrease the systemic toxicity of the pharmacological treatments. Two strategies have been used to achieve this folate receptor targeting: (i) the use of ligands with high affinity to FRs (e.g., folic acid or anti-FRs monoclonal antibodies) linked to the therapeutic agents or (ii) the use of nanocarriers whose surface is decorated with these ligands and in which the drug is encapsulated. This manuscript analyzes the use of FRs as a target to develop new therapeutic tools in the treatment of cancer and inflammatory diseases with an emphasis on the nanoformulations that have been developed for both therapeutic and imaging purposes.

Perspectives in Breast and Ovarian Cancer Chemotherapy by Nanomedicine Approach: Nanoformulations in Clinical Research.

BACKGROUND: Breast and ovarian carcinomas represent major health problems in women worldwide. Chemotherapy constitutes the main treatment strategy, and the use of nanocarriers, a good tool to improve it. Several nanoformulations have already been approved, and others are under clinical trials for the treatment of both types of cancers. OBJECTIVE: This review focuses on the analysis of the nanoformulations that are under clinical research in the treatment of these neoplasms. RESULTS: Currently, there are 6 nanoformulations in clinical trials for breast and ovarian carcinomas, most of them in phase II and phase III. In the case of breast cancer treatment, these nanomedicines contain paclitaxel; and, for ovarian cancer, nanoformulations containing paclitaxel or camptothecin analogs are being evaluated. The nanoencapsulation of these antineoplastics facilitates their administration and reduces their systemic toxicity. Nevertheless, the final approval and commercialization of nanoformulations may be limited by other aspects like lack of correlation between the efficacy results evaluated at in vitro and in vivo levels, difficulty in producing large batches of nanoformulations in a reproducible manner and high production costs compared to conventional formulations of antineoplastics. However, these challenges are not insurmountable and the number of approved nanoformulations for cancer therapy is growing. CONCLUSION: Reviewed nanoformulations have shown, in general, excellent results, demonstrating a good safety profile, a higher maximum tolerated dose and a similar or even slightly better antitumor efficacy compared to the administration of free drugs, reinforcing the use of nano-chemotherapy in both breast and ovarian tumors.

Development of Innovative Formulations for Breast Cancer Chemotherapy.

Breast cancer is the most frequent neoplasm in the female population [...].

Quimioterapia nanométrica a base de cannabinoides para el tratamiento de tumores ginecológicos / Cannabinoid based chemo-nanotherapy for the treatment of gynecological

El cannabidiol está despertando un creciente interés como agente antitumoral. Sin embargo, no se ha estudiado su efecto en cáncer de ovario, uno de los tumores más agresivos en mujeres. En el presente trabajo se ha evaluado, por primera vez, el potencial uso del cannabidiol en solución y encapsulado en nanopartículas funcionalizadas con ácido fólico en cáncer de ovario, ya que estos tumores sobre expresan los receptores de ácido fólico, permitiendo una acumulación selectiva de estas nanoformulaciones en las células tumorales. El cannabidiol en solución inhibe la proliferación y migración de las células SKOV-3. En terapia de combinación, aumenta significativamente la eficacia antitumoral del paclitaxel, presentando un efecto sensibilizador y sinérgico. En los modelos in ovo, la administración previa de cannabidiol en solución seguido de su coadministración con paclitaxel muestra un efecto inhibitorio sobre el crecimiento tumoral significativamente superior al paclitaxel en monoterapia. Las nanopartículas desarrolladas son eficazmente internalizadas por las células SKOV-3, presentando las nanopartículas con ácido fólico una captación más rápida. Aunque en los estudios de eficacia antitumoral in vitro las nanopartículas funcionalizadas no presentan una actividad antiproliferativa superior al cannabidiol en solución o a las nanopartículas no funcionalizadas, en los modelos in ovo su eficacia antitumoral es significativamente superior, indicando que el desarrollo de nanopartículas funcionalizadas con ácido fólico es una buena estrategia para vectorizar el cannabidiol a tumores de ovario. Por último, las nanopartículas de cannabidiol potencian el efecto antitumoral del paclitaxel, presentando las formulaciones funcionalizadas con ácido fólico una mayor eficacia que el cannabidiol en solución

Cannabidiol has become in a potential anticancer agent. Nevertheless, it has not been evaluated in ovarian cancer, one of the most aggressive tumors in women. In this work, the potential use of cannabidiol in solution and encapsulated into polymeric nanoparticles coated with folic acid was evaluated for the first time for the treatment of ovarian cancer. Ovarian tumors over-express folic acid receptors and folic-acid-coated nanoformulations trend to be selectively accumulated at tumor site. Cannabidiol in solution administered as monotherapy inhibits the proliferation and migration of SKOV-3 cells. In combination therapy, it significantly increases the antitumor efficacy of paclitaxel, showing a sensitizer and synergistic effect. In ovo, the previous administration of cannabidiol in solution followed by its co-administration with paclitaxel, shows a significantly higher inhibitory effect on ovarian tumor growth than single paclitaxel. The developed nanoparticles are efficiently uptaken by SKOV-3 cells, showing folic acid coated formulations a faster internalization. Although coated formulations do not exhibit a higher in vitro antiproliferative effect compared to cannabidiol in solution or non-coated formulations, in ovo its antitumoral efficacy is significantly higher. This indicates that folic acid-coated nanoparticles represent a good strategy to target cannabidiol to ovarian tumors. Finally, cannabidiol-loaded nanoparticles improve the in vitro antiproliferative effect of paclitaxel, showing folic acid-coated-formulations a better efficacy than cannabidiol in solution

Medical Use of Cannabinoids.

Cannabinoid receptors, endocannabinoids and the enzymes responsible for their biosynthesis and degradation constitute the endocannabinoid system. In recent decades, the endocannabinoid system has attracted considerable interest as a potential therapeutic target in numerous pathological conditions. Its involvement in several physiological processes is well known, such as in energy balance, appetite stimulation, blood pressure, pain modulation, embryogenesis, nausea and vomiting control, memory, learning and immune response, among others, as well as in pathological conditions where it exerts a protective role in the development of certain disorders. As a result, it has been reported that changes in endocannabinoid levels may be related to neurological diseases such as Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, as well as anorexia and irritable bowel syndrome. Alterations in the endocannabinoid system have also been associated with cancer, affecting the growth, migration and invasion of some tumours. Cannabinoids have been tested in several cancer types, including brain, breast and prostate cancers. Cannabinoids have shown promise as analgesics for the treatment of both inflammatory and neuropathic pain. There is also evidence for a role of the endocannabinoid system in the control of emotional states, and cannabinoids could prove useful in decreasing and palliating post-traumatic stress disorder symptoms and anxiolytic disorders. The role of the endocannabinoid system in addictions has also been examined, and cannabinoids have been postulated as alternative and co-adjuvant treatments in some abuse syndromes, mainly in ethanol and opioid abuses. The expression of the endocannabinoid system in the eye suggests that it could be a potential therapeutic target for eye diseases. Considering the importance of the endocannabinoid system and the therapeutic potential of cannabinoids in this vast number of medical conditions, several clinical studies with cannabinoid-based medications are ongoing. In addition, some cannabinoid-based medications have already been approved in various countries, including nabilone and dronabinol capsules for the treatment of nausea and vomiting associated with chemotherapy, dronabinol capsules for anorexia, an oral solution of dronabinol for both vomiting associated with chemotherapy and anorexia, a Δ9-tetrahydrocannabinol/cannabidiol oromucosal spray for pain related to cancer and for spasticity and pain associated with multiple sclerosis, and an oral solution of cannabidiol for Dravet and Lennox-Gastaut syndromes. Here, we review the available efficacy, safety and tolerability data for cannabinoids in a range of medical conditions.

Effects of cannabidiol plus naltrexone on motivation and ethanol consumption.

BACKGROUND AND PURPOSE: The aim of this study was to explore if the administration of naltrexone together with cannabidiol (CBD) may improve the efficacy in reducing alcohol consumption and motivation rather than any of the drugs given separately. EXPERIMENTAL APPROACH: The effects of low doses of naltrexone (0.7 mg·kg-1 , p.o.) and/or CBD (20 mg·kg-1 ·day-1 , s.c.) on ethanol consumption and motivation to drink were evaluated in the oral-ethanol self-administration paradigm in C57BL/6 mice. Gene expression analyses of the opioid µ receptor (Oprm1) in the nucleus accumbens (NAc), tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and the 5-HT1A receptor in the dorsal raphe nucleus (DR) were carried out by real-time PCR. The role of 5-HT1A receptors in the ethanol reduction induced by the administration of CBD + naltrexone was analysed by using the 5-HT1A receptor antagonist WAY100635 (0.3 mg·kg-1 , i.p.). KEY RESULTS: The administration of CBD + naltrexone significantly reduced motivation and ethanol intake in the oral self-administration procedure in a greater proportion than the drugs given alone. Only the combination of both drugs significantly reduced Oprm1, TH and 5-HT1A gene expressions in the NAc, VTA and DR respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD + naltrexone but had no effects by itself. CONCLUSION AND IMPLICATIONS: The combination of low doses of CBD plus naltrexone were more effective than either CBD or naltrexone alone at reducing ethanol consumption and the motivation to drink. These effects appear to be mediated, at least in part, by 5-HT1A receptors.

Insights into the effects of the endocannabinoid system in cancer: a review.

In the last few decades, the endocannabinoid system has attracted a great deal of interest in terms of its applications to clinical medicine. In particular, its applications in cancer probably represent one of the therapeutic areas with most promise. On the one hand, expression of the endocannabinoid system is altered in numerous types of tumours, compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type. On the other hand, cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells and also tumour angiogenesis. However, some cannabinoids, at lower concentrations, may increase tumour proliferation, inducing cancer growth. Enough data has been provided to consider the endocannabinoid system as a new therapeutic target in cancer, although further studies to fully establish the effect of cannabinoids on tumour progression are still needed.

Enmascaramiento de sabores en formas farmacéuticas sólidas orales / Taste masking in oral solid dosage forms

Aunque tradicionalmente ligado a formas farmacéuticas líquidas orales, el enmascaramiento del sabor como parámetro crítico en la formulación de medicamentos ha cobrado recientemente un nuevo auge en respuesta al desarrollo de formas farmacéuticas sólidas orales que persiguen una disgregación, bien ex vivo, bien en la cavidad bucal. El enmascaramiento no sólo comprende la neutralización del potencial sabor desagradable inherente al principio activo, sino también la obtención de un sabor agradable en la formulación final, con repercusión tanto a nivel sanitario, puesto que cuanto mayor sea la aceptación por parte del paciente, mayor será su adherencia al tratamiento; como a nivel económico, ya que el sabor del producto puede marcar la diferencia entre el éxito y el fracaso comercial. Mediante esta revisión se ponen de relieve las estrategias aplicables en el enmascaramiento de sabores de formas farmacéuticas sólidas orales, se clasifican y describen los principales excipientes correctores del sabor, así como se efectúa una compilación exhaustiva de las técnicas de evaluación de la eficacia de los distintos recursos empleados en el enmascaramiento del sabor desagradable. De esta forma, se amplía el ámbito de aplicación del concepto enmascaramiento del sabor, demostrándose que es un área del cual aún hay mucho por decir

Despite being traditionally associated with oral liquid dosage forms, taste masking as critical attribute in the formulation of drug products has recently experienced a renaissance, mostly due to the development of oral solid dosage forms aimed at achieving disintegration either under ex vivo conditions or even more relevantly into the oral cavity. Not only does taste masking involve the neutralization of the potential unpleasant flavour inherent to the drug substance, but also seeks to achieve tasty flavour in the final drug product, since it has influence both to a sanitary extent (the higher the patient acceptance, the better the patient compliance) and to an economical extent (since the flavour of a marketed product can make the difference between commercial success or commercial failure). The purpose of this review is to outline the strategies likely to be applied in taste masking of oral solid dosage forms, to sort out and describe the major flavour-modifying agents in the pharmaceutical field, as well as to compile comprehensively testing techniques of the efficacy of the various taste masking strategies. Consequently, this review adds to the scope of taste masking a further dimension, serving thus as a proof-of-concept that much remains still to be said in this area

Cannabinoides: una prometedora herramienta para el desarrollo de nuevas terapias / Cannabinoids: a promissing tool for the development of novel therapies

Los cannabinoides, mediadores lipídicos presentes en la planta Cannabis sativa, han sido utilizados en medicina desde la antigüedad; retirándose del arsenal terapéutico en la primera mitad del siglo XX debido a sus efectos adversos psicoactivos y a la aparición de alternativas más seguras. No obstante el descubrimiento del sistema cannabinoide endógeno y su participación reguladora en múltiples funciones fisiológicas básicas del organismo suscitaron de nuevo a finales del siglo pasado el interés de los investigadores como posibles herramientas terapéuticas en diversas patologías como trastornos neurodegenerativos y metabólicos, enfermedades autoinmunes, glaucoma e, incluso, cáncer

Cannabinoids, lipid mediators presents in Cannabis sativa plant, have been used for medicinal purposes for centuries. In the first half of the twentieth century they were removed from medicine due to their psychoactive adverse effects and the emergence of safer drugs. Nevertheless at the end of this century the discovery of endogenous cannabinoid system and its participation in multiple basic physiological functions have attracted much attention to the researchers as possible tools in the treatment of several pathological conditions such as neurodegenerative and metabolic disorders, autoimmune diseases, glaucoma and cancer