Formulaciones microbicidas para la prevención de la transmisión sexual del vih

El VIH es uno de los principales problemas de salud pública a nivel mundial, especialmente en los países más desfavorecidos. Hay que destacar la situación en que se encuentran las mujeres, pues en muchos países es habitual la violencia sexual contra jóvenes y niñas y las medidas de prevención de la transmisión no están bajo su control. Cada año 380.000 mujeres de entre 10 y 24 años contraen la infección por VIH, y el 80% de ellas viven en el África subsahariana. Por este motivo, es necesario disponer de métodos de prevención controlados por las mujeres, como los microbicidas. En este trabajo se ha recopilado y analizado la información más relevante de la que se dispone actualmente con respecto a las formulaciones microbicidas para prevenir la transmisión sexual del VIH. Con los resultados disponibles hasta la fecha, se puede afirmar que los surfactantes han sido rápidamente descartados como microbicidas, por su falta de eficacia protectora. Entre todos los inhibidores de la entrada del virus estudiados, los más prometedores son aquellos que incluyen un fármaco antiviral, como el Maraviroc, o anticuerpos monoclonales inhibidores de la glicoproteína 120. Los microbicidas que incluyen inhibidores de la transcriptasa inversa, como el Tenofovir, son los que mejor eficacia protectora han mostrado hasta la fecha. Los probióticos han surgido recientemente como potenciales microbicidas, pero aún se encuentran en fases tempranas de desarrollo. Se puede concluir que los microbicidas son una herramienta prometedora para prevenir la transmisión sexual del VIH, pero aún queda un largo camino por recorrer pues se trata de un campo con amplio margen de mejora

Design, development and evaluation of vaginal administration formulations for the prevention of HIV sexual transmission

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 01-12-2020La infección por el virus de inmunodeficiencia humana (VIH) es un problema de salud pública a nivel mundial, pero su incidencia es particularmente preocupante entre las mujeres jóvenes de países de bajos y medios ingresos. Diversos factores predisponen a este grupo poblacional a estar más expuesto al contagio, tales como la violencia sexual, la pobreza y la falta de poder de decisión sobre su propia salud sexual. Son estas circunstancias las que han llevado al estudio de los microbicidas vaginales como una herramienta para prevenir la transmisión sexual del virus. Los primeros microbicidas fueron diseñados para una administración diaria, pero la falta de frecuencia en su uso observada en ensayos clínicos llevó a la búsqueda de formas farmacéuticas que permitieran una posología más cómoda. En la actualidad, la investigación en el campo de los microbicidas vaginales sigue siendo particularmente intensa, explorándose el uso de formas farmacéuticas alternativas, la cada vez más presente aplicación de nanosistemas para la liberación de fármacos, o incluso el uso de probióticos modificados genéticamente para la expresión de sustancias con potencial viricida. A pesar de ello, el desarrollo de microbicidas vaginales aún tiene un largo camino por recorrer, como demuestra el hecho de que todavía no exista ningún producto comercializado para este fin...The infection by human immunodeficiency virus (HIV) is a global public health problem, but its incidence is particularly worrisome in women from low- and middle-income countries. Several factors predispose this population group to be more exposed to sexual acquisition of the virus, such as the frequency of sexual violence, poverty and the lack of decision-making power over their own sexual health. These circumstances have led to the study of vaginal microbicides as a tool to prevent the sexual transmission of the virus.The first microbicides developed were designed for daily administration, but the low frequency of use led to the search for pharmaceutical forms that allow a most convenient dosage. Currently, research in the field of vaginal microbicides continues to be particularly intense, looking into alternative pharmaceutical forms, the application of nanosystems for drug delivery, or even the use of genetically modified probiotics for the release of viricidal substances. Despite this, the development of vaginal microbicides still has a long way to go, as evidenced by the fact that there are still no commercialised products for this purpose...Fac. de FarmaciaTRUEunpu

Vaginal Formulations for Prevention of Sexual Transmission of HIV

According to UNAIDS, as there is still no effective vaccine against HIV, pre-exposure prophylasis (PrEP) is necessary to reduce its incidence. Sexual transmission rate is higher from men to women in developing countries and vertical transmission may also occur from mother to child. Hence, vaginal formulations are an interesting proposal for the protection of women, preventing the virus from infecting vagina through different mechanisms. Several drugs, such as Dapivirine, Tenofovir or Maraviroc, have been assessed and showed to be effective in this field. These microbicides are included in different dosage forms able to release the drug once in contact with the vaginal medium. Innovative excipients are being employed for the development of different systems trying to get an easier posology through control release and high comfortability, thus leading to a better compliance. In this line, several formulations have been developed and tested, such as rings, tablets, gels or films. Some of them are nowadays in clinical trials, such as a Tenofovir gel or a Dapivirine vaginal ring. The aim of this chapter is to synthetize the research and findings in the field of the development and assessment of vaginal formulations in the PrEP of HIV sexual transmission

Eudragit® L100/chitosan composite thin bilayer films for intravaginal pH-responsive release of Tenofovir

[EN] The high rate of HIV new infections and AIDS-related deaths each year make prevention tools still necessary today. Different dosage forms – including films – for vaginal administration of antiretroviral drugs have been developed for this purpose. Six batches of Tenofovir-loaded films were formulated based on Eudragit® L100 (EL100) and chitosan, containing triethyl citrate and glycerol. In all the cases films structured in two layers – the upper layer mainly attributed to EL100 and the lower layer to chitosan – were revealed by SEM. A higher content in EL100 and plasticizers improves the mechanical properties and control over drug release in the vaginal medium without affecting mucoadhesion. The EL100-based layer acts as a structuring agent that controls Tenofovir release for days in the vaginal medium while it occurs in a few hours in the presence of seminal fluid. Bilayer films with the highest tested content of EL100 and plasticizers would be the most suitable as vaginal microbicides as they are easier to administer due to their excellent mechanical properties and they offer more comfortable posology and enhanced protection against HIV during intercourse due to their pH-responsive release of Tenofovir.This work was supported by the Spanish Research Agency and the European Regional Development Fund (AEI/FEDER, UE) [MAT2016-76416-R]

Amino Functionalized Micro-Mesoporous Hybrid Particles for the Sustained Release of the Antiretroviral Drug Tenofovir

© 2020 by the authors.The sustained release of an antiretroviral agent to women mucosa has been proved as an excellent strategy to reduce the sexual transmission of HIV. Hybrid micro-mesoporous particles have been synthesized and functionalized with a silane coupling agent followed by loading the antiretroviral tenofovir. It has been observed that the disposition of the silane molecule on the surface of the particles determines the interaction mechanism with the antiretroviral molecule loaded independently on the surface area of the particles. In this sense, available and free amino groups are required to achieve a smart pH-responsive material, a condition that is only achieved in those materials containing a silane chemisorbed monolayer. Moreover, the modulation of the release kinetics attributed to the presence of the silane monolayer covering the mesopores has been confirmed by fitting the releasing curves to the first order and Weibull models. The developed micro-mesoporous particles have been demonstrated to be excellent smart-release vehicles for antiviral agents and can be safely used in polymer mucoadhesive vaginal gels.This work was supported by the Spanish Research Agency and the European Regional Development Fund (AEI/FEDER, UE), grant number MAT2016-76416-R.Peer reviewe

Silane Modification of Mesoporous Materials for the Optimization of Antiviral Drug Adsorption and Release Capabilities in Vaginal Media

Three different functionalities have been incorporated into mesoporous materials by means of a coupling reaction with the siloxanes 3-glycidoxypropyl-trimethoxysilane (GLYMO), 3-methacryloxypropyl-trimethoxysilane (MEMO), and 3-mercaptopropyl-trimethoxysilane (MPTMS). The disposition of the different functional groups, as well as the interaction mechanism, with the mesoporous substrate has been identified. The amount of the antiviral drug acyclovir (ACV) adsorbed depends not only on the available surface area but also on the chemical or physicochemical interactions between functionalities. The drug adsorption isotherm of the materials functionalized with GLYMO and MPTMS follow mechanisms dependent on the different surface coverage and the possibilities to establish physicochemical interactions between the drug molecule and the functionalities. On the contrary, when functionalizing with MEMO, the dominant adsorption mechanism is characteristic of chemically bonded adsorbates. The ACV release kinetics is best fitted to the Weibull model in all the functionalized materials. When the MTPMS is used as a functionalizing agent, the drug diffusion occurs at low kinetics and homogeneously along the mesoporous channels

Bigels as drug delivery systems: From their components to their applications

Bigels are systems that usually result from mixing a hydrogel and an organogel: the aqueous phase is commonly formed by a hydrophilic biopolymer, whereas the organic phase comprises a gelled vegetable oil because of the presence of an organogelator. The proportion of the corresponding gelling agent in each phase, the organogel/hydrogel ratio, and the mixing temperature and speed all need to be taken into consideration for bigel manufacturing. Bigels, which are particularly useful drug delivery systems, have already been formulated for transdermal, buccal, and vaginal routes. Mechanical assessments and microscopy are the most reported characterization techniques. As we review here, their composition and unique structure confer promising drug delivery attributes, such as mucoadhesion, the ability to control drug release, and the possibility of including both hydrophilic and lipophilic drugs in the same system

Long-term etanercept survival in patients with psoriatic arthritis: a multicenter retrospective analysis in daily clinical practice in Spain

Although several randomized clinical trials and observational studies have evaluated the effectiveness, safety and drug survival of etanercept (ETN) in the treatment of psoriatic arthritis (PsA), long-term data regarding these aspects are currently scarce. For this reason, we sought to investigate the long-term survival and safety of ETN in PsA patients in 4 tertiary care Spanish hospitals over a 13-year observation period (from 2004 to 2017). The records of 85 PsA patients were reviewed. ETN showed an excellent survival profile, with rates of treatment discontinuation at 1, 3, 5 and 10 years of 15, 37, 46 and 59%, respectively. In our cohort, a trend toward longer drug survival in patients with shorter disease duration and those who were treated with ETN as their first biologic agent was observed. On the other hand, combination therapy with conventional disease-modifying antirheumatic drugs did not provide greater improvement on the long-term drug survival. Only 12% of the patients reported adverse events (AEs) during therapy, being most of them of mild to moderate intensity, and in only 7% AEs led to drug discontinuation. To the best of our knowledge, the present study shows the largest follow-up period of ETN-treated population analyzed in a real-life setting, and these results demonstrate the positive safety profile and long-term effectiveness of this biologic agent in the management of PsA patients

Informe de investigación COVID19: Voces de docentes y familias

Proyecto Atlántid