Recent advances in the mucus-interacting approach for vaginal drug delivery: from mucoadhesive to mucus-penetrating nanoparticles

Rossi, Silvia; Vigani, Barbara; Sandri, Giuseppina; Caramella, Carla; Ferrari, Franca

doi:10.1080/17425247.2019.1645117

Cited by 39 publications

(27 citation statements)

References 35 publications

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“…This poses a challenge for the development of vaginal products. The vagina is an imperative alternative site to deliver drugs locally and systemically, attributed to the high exposure of the contact surface, dense vascularization, and avoidance of gastrointestinal environment and hepatic first-pass effect [12][13][14]. However, some concerns have arisen regarding the eligibility of the vagina as a route for administration due to its highly variable microenvironment contributed to by the alterations in vaginal microbiota and the chemical changes such as pH, vaginal fluids, and vaginal mucus [12,14,15].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The cervicovaginal mucus (CVM) mixture is also known as the vaginal fluid is constituted by cervical mucus and cervicovaginal fluid [13]. Vaginal fluid acts as a barrier to protects the vagina against infection by trapping the pathogenic microbes [12,13]. However, the properties of the vaginal fluid vary by age, vaginal flora, vaginal practices, sexual intercourse, pathological conditions and throughout the menstrual cycle [12,14,15].…”

Section: Introductionmentioning

confidence: 99%

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Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

et al. 2020

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An optimal host–microbiota interaction in the human vagina governs the reproductive health status of a woman. The marked depletion in the beneficial Lactobacillus sp. increases the risk of infection with sexually transmitted pathogens, resulting in gynaecological issues. Vaginal infections that are becoming increasingly prevalent, especially among women of reproductive age, require an effective concentration of antimicrobial drugs at the infectious sites for complete disease eradication. Thus, topical treatment is recommended as it allows direct therapeutic action, reduced drug doses and side effects, and self-insertion. However, the alterations in the physiological conditions of the vagina affect the effectiveness of vaginal drug delivery considerably. Conventional vaginal dosage forms are often linked to low retention time in the vagina and discomfort which significantly reduces patient compliance. The lack of optimal prevention and treatment approaches have contributed to the unacceptably high rate of recurrence for vaginal diseases. To combat these limitations, several novel approaches including nano-systems, mucoadhesive polymeric systems, and stimuli-responsive systems have been developed in recent years. This review discusses and summarises the recent research progress of these novel approaches for vaginal drug delivery against various vaginal diseases. An overview of the concept and challenges of vaginal infections, anatomy and physiology of the vagina, and barriers to vaginal drug delivery are also addressed.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

et al. 2020

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“…The administration of drugs to the vaginal site has proven advantageous for both local and systemic therapy thanks to the possibility of self-administration, the potential of prolonged treatment due to long residence time of the drug in loco , and the avoidance of first-pass metabolism in the case of systemic therapies [ 1 ]. Research efforts have been directed towards the development of drug formulations for treating vaginal infections, sexually transmitted diseases, cervical cancer, and hormonal contraception [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

et al. 2020

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Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection/pre-puberty/post-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations.

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“…In the case of application on a mucosa, it is desirable that in situ gelling drug-delivery systems possess mucoadhesive properties; that is the capability to interact with mucus and, thus, to further prolong the formulation residence time [ 3 ]. A recent novel strategy to achieve a prolonged drug permanence into the administration site and an enhanced drug diffusion across the mucus is represented by dual-functioning formulations composed of nanosystems (NSs) loaded into a mucoadhesive in situ gelling vehicle, able to release NSs after administration [ 12 ]. The mucoadhesive in situ gelling vehicle has the function to create an intimate contact with the mucus, providing a greater retention of the loaded NSs at the administration site, whereas the NSs do not bind to mucus components but should be able to cross the mucus barrier, reaching the mucosal surface that represents their site of action/absorption.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

et al. 2020

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In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies.

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Recent advances in the mucus-interacting approach for vaginal drug delivery: from mucoadhesive to mucus-penetrating nanoparticles

Cited by 39 publications

References 35 publications

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

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