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•Bigels are systems that usually result from mixing a hydrogel and an organogel.•A hydrophilic biopolymer is commonly the structuring agent of the aqueous phase.•An organogelator ...causes the vegetable oil to be gelled forming the organogel.•Factors like organogel/hydrogel ratio condition bigels features and drug release.•Bigels for transdermal, buccal and vaginal drug delivery have been developed.
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.
The continuous advances in surgical procedures require continuous research regarding materials with surgical applications. Biopolymers are widely studied since they usually provide a biocompatible, ...biodegradable, and non-toxic material. Among them, chitosan is a promising material for the development of formulations and devices with surgical applications due to its intrinsic bacteriostatic, fungistatic, hemostatic, and analgesic properties. A wide range of products has been manufactured with this polymer, including scaffolds, sponges, hydrogels, meshes, membranes, sutures, fibers, and nanoparticles. The growing interest of researchers in the use of chitosan-based materials for tissue regeneration is obvious due to extensive research in the application of chitosan for the regeneration of bone, nervous tissue, cartilage, and soft tissues. Chitosan can serve as a substance for the administration of cell-growth promoters, as well as a support for cellular growth. Another interesting application of chitosan is hemostasis control, with remarkable results in studies comparing the use of chitosan-based dressings with traditional cotton gauzes. In addition, chitosan-based or chitosan-coated surgical materials provide the formulation with antimicrobial activity that has been highly appreciated not only in dressings but also for surgical sutures or meshes.
Films have undoubtedly seen the most significant advances in their development in recent years of all the pharmaceutical forms for the vaginal administration of drugs. Films combine the advantages of ...gels and solid pharmaceutical forms, and their great versatility is largely determined by the numerous polymers that can be used for their fabrication. They may be based on many natural polymers, and cellulose derivatives, polyvinyl alcohol or acrylic derivatives – among others – are also frequently used. The combination of different polymers and the inclusion of plasticizing agents makes them extremely versatility for responding to a range of therapeutic needs. The techniques used to produce films have also undergone substantial development. Although the solvent casting technique is by far the most widely used in fabrication, alternative options have also emerged such as electrospinning, moulding extrusion and 3D printing. Various research groups have proposed a proliferation of assays to characterise vaginal films in recent years, which highlight the importance of the preliminary evaluation and determination of the films' uniformity, in addition to tests to determine their permeability and hydrophilic/hydrophobic coefficient and their mechanical properties, the application of imaging techniques and thermal analysis, and especially the evaluation of the mucoadhesive properties and control over the drug release. This article offers a critical overview of the advances in the development and fabrication of films intended for vaginal drug delivery, and summarises current clinical applications for vaginal films.
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•Film technology provides platforms adaptable to the desired drug release profile.•Several natural and synthetic polymers have been considered to obtain vaginal films.•Plasticisers and other excipients allow modifying the relevant properties of films.•Solvent casting is the most common manufacturing method, but others are emerging.•Films could be useful against STDs, unintended pregnancy and other FGT disorders.
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.
Vaginal films featuring the pH-dependent release of tenofovir (TFV) were developed for the prevention of sexual transmission of human immunodeficiency syndrome (HIV). Films based on hydroxypropyl ...methylcellulose and zein were prepared incorporating different plasticizers oleic acid, lactic acid, glycerol, and polyethylene glycol 400 (PEG) and evaluated for in vitro drug release in an acidic simulated vaginal fluid (pH 4.2) and a slightly alkaline mixture of simulated seminal and vaginal fluids (pH 7.5). Results revealed that optimal biphasic TFV release was possible with proper combination of plasticizers (PEG and oleic acid, 1:7 w/w) and by adjusting the plasticizer/matrix-forming material ratio. The films had similar or higher levels of TFV associated with genital epithelial cells (Ca Ski or HEC-1-A cells) but lower drug permeability compared to the free drug. These data confirm that films have the potential to achieve suitable mucosal levels of TFV with low systemic exposure. The films developed could protect women from HIV sexual transmission.
Women are still at high risk of contracting the human immunodeficiency virus (HIV) virus due to the lack of protection methods under their control, especially in sub-Saharan countries. ...Polyelectrolyte multilayer smart vaginal films based on chitosan derivatives (chitosan lactate, chitosan tartate, and chitosan citrate) and Eudragit
S100 were developed for the pH-sensitive release of Tenofovir. Films were characterized through texture analysis and scanning electron microscopy (SEM). Swelling and drug release studies were carried out in simulated vaginal fluid and a mixture of simulated vaginal and seminal fluids. Ex vivo mucoadhesion was evaluated in bovine vaginal mucosa. SEM micrographs revealed the formation of multilayer films. According to texture analysis, chitosan citrate was the most flexible compared to chitosan tartrate and lactate. The swelling studies showed a moderate water uptake (<300% in all cases), leading to the sustained release of Tenofovir in simulated vaginal fluid (up to 120 h), which was accelerated in the simulated fluid mixture (4-6 h). The films had high mucoadhesion in bovine vaginal mucosa. The multilayer films formed by a mixture of chitosan citrate and Eudragit
S100 proved to be the most promising, with zero toxicity, excellent mechanical properties, moderate swelling (<100%), high mucoadhesion capacity, and Tenofovir release of 120 h and 4 h in vaginal fluid and the simulated fluid mixture respectively.
Young women in sub-Saharan Africa have the highest risk of human immunodeficiency virus (HIV) acquisition through sexual contact of all groups. Vaginal controlled release of antiretrovirals is a ...priority option for the prevention of sexual transmission of the virus in women. In this manuscript, bilayer films were prepared based on ethylcellulose and a natural polymer (xanthan or tragacanth gum) plasticized with glycerol and tributylcitrate for tenofovir-controlled release. The mechanical properties and microstructure of the blank films were characterized by texture analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The loaded films were evaluated in simulated vaginal fluid through release and swelling studies and
mucoadhesion assessments. The results show that the preparation method produced bilayer films with adequate mechanical properties. The contribution of both layers allowed the sustained release of tenofovir and a mucoadhesion time of up to 360 h. The toxicity of the materials was evaluated in three cell lines of vaginal origin. The films constituted by ethylcellulose and xanthan gum in a 2:1 proportion (EX2-D) showed the longest mucoadhesion time, with 15 days of tenofovir-controlled release, zero toxicity, and optimal mechanical properties. These films are therefore a promising option for offering women a means of self-protection against the sexual transmission of HIV.
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Although vaginal films were initially developed for a fast release of the drug, with the adequate formulation they can also be useful for sustained release. The latest strategies for ...the prevention of the sexual transmission of HIV have moved towards sustained-release dosage forms, so films may be an effective strategy that could also improve the patient’s comfort. A hydrophilic polymer (hydroxypropylmethyl cellulose) and an amphiphilic polymer (zein) have been evaluated for the development of Tenofovir sustained-release vaginal films. The modification of the film’s properties by the inclusion of polar (glycerol and polyethylene glycol 400 (PEG)) and amphiphilic (tributyl citrate and oleic acid) plasticisers was also evaluated. The films’ physicochemical and mechanical properties were determined. The in vitro release of Tenofovir from the films and their bioadhesive capacity and behaviour in simulated vaginal fluid were also assessed. The combination of hydroxypropylmethyl cellulose and zein in films (ratio 1:5), with the inclusion of PEG (40% w/w) proved not only to have excellent mechanical properties, but was also able to release TFV in a sustained manner for 120 h and remain attached to biological tissues throughout this time. This film could be an interesting option for the prevention of sexual transmission of HIV.
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Electrospinning is an innovative technique that allows production of nanofibers and microfibers by applying a high voltage to polymer solutions of melts. The properties of these ...fibers – which include high surface area, high drug loading capacity, and ability to be manufactured from mucoadhesive polymers – may be particularly useful in a myriad of drug delivery and tissue engineering applications. The last decade has witnessed a surge of interest in the application of electrospinning technology for the fabrication of vaginal drug delivery systems for the treatment and prevention of diseases associated with women's sexual and reproductive health, including sexually transmitted infections (e.g. infection with human immunodeficiency virus and herpes simplex virus) vaginitis, preterm birth, contraception, multipurpose prevention technology strategies, cervicovaginal cancer, and general maintenance of vaginal health. Due to their excellent mechanical properties, electrospun scaffolds are also being investigated as next-generation materials in the surgical treatment of pelvic organ prolapse. In this article, we review the latest advances in the field.
Interest is growing in “smart” vaginal microbicides as a strategy to protect women from sexual transmission of human immunodeficiency virus (HIV). The concept is based on the development of products ...featuring low drug release in acidic media such as vaginal fluid but switch to a fast release profile when the medium becomes neutral or slightly alkaline. This mimics the surge in pH occurring in the vagina after sexual intercourse due to the seminal fluid. Semen is the main vehicle for HIV-1, and increasing antiretroviral drug levels in the vagina upon ejaculation may contribute to enhanced protection against viral sexual transmission. This work explores the use of different pharmaceutical-grade methacrylic acid-based polymers (EudragitⓇ RL, RS, L and S) for developing vaginal films allowing the pH-dependant release of the antiretroviral drug tenofovir (TFV). EudragitⓇ L 100 and EudragitⓇ S 100, containing triethyl citrate as plasticiser, proved to be suitable for manufacturing films with optimal dual in vitro drug-release behaviour. TFV-release can be sustained for several days after film administration and all the drug is released in a few hours in conditions simulating ejaculation. The films’ mechanical properties were also deemed suitable for comfortable vaginal administration. Two optimized films were further assessed using HEC-1-A and Ca Ski cell monolayer models and were found to possess favourable drug permeability profiles and drug levels associated to cell monolayer as compared to free TFV. Overall, pH-dependant films containing tenofovir may constitute promising candidates for “smart” vaginal microbicides to protect women from sexual HIV transmission.
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