Formulaciones de administración vaginal para la prevención del herpes genital

El herpes genital, producido por el Virus Herpes Simplex (VHS) tipo 2, es una de las enfermedades de transmisión sexual más extendida a nivel mundial. La ineficacia de los sistemas actuales de prevención hace necesario desarrollar nuevas formulaciones, siendo las más estudiadas aquellas que permanecen adheridas en la zona de aplicación y que permitan una liberación sostenida de agentes microbicidas. Por ello, el objetivo de este trabajo es realizar una revisión bibliográfica para comparar los distintos polímeros empleados como excipientes en dichas formulaciones así como la evaluación de los métodos de caracterización in vitro y ex vivo de las mismas. Los polímeros empleados frecuentemente en formulaciones mucoadhesivas vaginales pueden ser de origen natural, sintéticos y semisintéticos. Estos excipientes se emplean con el fin de conseguir formulaciones mucoadhesivas que además modulen la liberación de agentes microbicidas a nivel vaginal, y estas propiedades van a ser directamente dependientes de las características del polímero utilizado. Los sistemas preparados se someten a varios ensayos in vitro que permitan caracterizar sus propiedades. Así, el hinchamiento se evalúa con el fin de determinar las propiedades estructurales del polímero en la formulación, lo cual condiciona los dos estudios siguientes; los de mucoadhesión y los de cesión, que permiten comprobar que la formulación permanece en la zona de aplicación el tiempo necesario y que la cesión del agente microbicida es constante durante el periodo de permanencia en la mucosa

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

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

Natural polymer-based solid mucoadhesive vaginal formulations for sustained microbicide release for prevention of sexuality transmitted HIV

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 01-10-2021En ausencia de una vacuna eficaz frente al virus de la inmunodeficiencia humana (VIH), el Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA) recomienda el desarrollo productos estables, seguros, efectivos y aceptables que puedan reducir con éxito la transmisión sexual de este virus. La profilaxis preexposición mediante formulaciones de administración vaginal puede ser útil para este objetivo, ya que aporta a las mujeres una opción de autoprotección sin necesidad del consentimiento de la pareja sexual. Sin embargo, ensayos clínicos con microbicidas de administración vaginal han fallado en su propósito debido a una baja adherencia al tratamiento al ser necesaria una administración diaria. En el presente trabajo de tesis se propone el desarrollo y la evaluación de formulaciones vaginales basadas en polímeros naturales para la liberación sostenida de fármacos antirretrovirales...In the absence of an effective vaccine against the human immunodeficiency virus (HIV), the Joint United Nations Program on HIV/AIDS (UNAIDS) recommends the development of stable, safe, effective and acceptable products that can successfully reduce the HIV sexual transmission. The pre-exposure prophylaxis through vaginal administered formulations can be useful for this purpose, since it provides women with an option of self-protection without the need of permission of the sexual partner. However, most clinical trials with microbicides for vaginal administration have failed in their purpose due to low adherence to treatments caused by the need of daily administration. This thesis purposes the development and characterization of vaginal formulations based on natural polymers for the sustained release of antiretroviral drugs...Fac. de FarmaciaTRUEunpu

Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir during Intercourse

Sub-Saharan African women are still at risk from the human immunodeficiency virus (HIV), and sex with men is the main route of transmission. Vaginal formulations containing antiretroviral drugs are promising tools to give women the power to protect themselves. The aim of this work was to obtain freeze-dried bigels containing pectin, chitosan, or hypromellose for the vaginal controlled release of Tenofovir, which is accelerated in the presence of semen. Nine batches of bigels were formulated using different proportions of these polymers in the hydrogel (1, 2, and 3% w/w). The bigels obtained were freeze-dried and then underwent hardness and deformability, mucoadhesion, swelling, and drug release tests, the last two in simulated vaginal fluid (SVF) and SVF/simulated seminal fluid (SSF) mixture. The formulation containing 3% pectin (fd3P) has the highest values for hardness, resistance to deformation, and good mucoadhesivity. Its swelling is conditioned by the pH of the medium, which is responsive to the controlled release of Tenofovir in SVF, with the fastest release in the SVF/SSF mixture. fd3P would be an interesting smart microbicidal system to allow faster release of Tenofovir in the presence of semen, and thus increase women’s ability to protect themselves from the sexual transmission of HIV

Naturally Occurring Polyelectrolytes and Their Use for the Development of Complex-Based Mucoadhesive Drug Delivery Systems: An Overview

Biopolymers have several advantages for the development of drug delivery systems, since they are biocompatible, biodegradable and easy to obtain from renewable resources. However, their most notable advantage may be their ability to adhere to biological tissues. Many of these biopolymers have ionized forms, known as polyelectrolytes. When combined, polyelectrolytes with opposite charges spontaneously form polyelectrolyte complexes or multilayers, which have great functional versatility. Although only one natural polycation—chitosan has been widely explored until now, it has been combined with many natural polyanions such as pectin, alginate and xanthan gum, among others. These polyelectrolyte complexes have been used to develop multiple mucoadhesive dosage forms such as hydrogels, tablets, microparticles, and films, which have demonstrated extraordinary potential to administer drugs by the ocular, nasal, buccal, oral, and vaginal routes, improving both local and systemic treatments. The advantages observed for these formulations include the increased bioavailability or residence time of the formulation in the administration zone, and the avoidance of invasive administration routes, leading to greater therapeutic compliance