Advanced Drug Delivery Reviews 92 (2015) 1
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr
Editorial
Special issue on vaginal drug delivery Rita Palmeira de Oliveira a,b, José Martinez de Oliveira a,c, Carla Caramella d a
CICS-Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal Pharmacy Department, Centro Hospitalar Cova da Beira, Covilhã, Portugal c Child and Women's Health Department, Centro Hospitalar Cova da Beira, Covilhã, Portugal d Department of Drug Sciences, University of Pavia, Pavia, Italy b
Whereas in the past the vagina was considered to be a passive organ, being part of the female reproductive apparatus, nowadays its relevance as a functional organ is consensual, and its role under different aspects, from sexuality to homeostasis, is recognized. It is, so, natural, that vaginal drug delivery has evolved from an almost exclusive local form of therapy to a broader route of drug delivery to either treat or prevent diseases and to allow for controlled or enhanced drug absorption. All these new therapeutic possibilities do take advantage of the unique anatomical and physiological features of the female reproductive organ that results in a systemic delivery of drugs avoiding hepatic first pass effect and gastrointestinal interferences while assuring, in accordance with the chosen formulation, high and/or stable local concentrations and reduced, enhanced and/or controlled systemic absorption. Simultaneously, the large investment in research related to prevention of sexually transmitted diseases has brought new insights in understanding vaginal pharmacokinetics and pharmacodynamics in the context of the development of microbicides. This issue on Vaginal Drug Delivery aims to provide an overview of recent developments in this field either for local or systemic, therapeutic or preventive strategies. New technological approaches of traditionally unsolved limitations as well as new perspectives and potentials of the vaginal route are addressed. Performance issues are also discussed concerning vaginal formulations and in vitro, ex vivo and in vivo tests both for safety and efficacy assessments of vaginal products are reviewed. Finally, an important focus is given to consumer's opinions, through evaluating women's perspectives, preferences and adherence concerning vaginal dosage forms, particularly in the context of contraceptives and microbicides, since their consistent and correct use represents a main factor for efficacy and must be carefully considered for the development of successful vaginal products. Planned under a logical sequence, the first papers address the physiological basis of vaginal drug delivery and the methodologies for preclinical characterization of vaginal formulations. Katz et al. (Vaginal drug distribution modeling) explain the importance of drug distribution modeling in the vaginal environment as a tool to predict drug delivery to the vaginal lumen and drug transportation through the vaginal walls with a specific focus on dosage form determinants. In the second review, Machado et al. address the in vitro, ex vivo and in vivo methodologies used to study drug permeation through the vaginal walls (Studies and methodologies on vaginal drug permeation), and following, and due to the particular interest of microbicides design and characterization in
http://dx.doi.org/10.1016/j.addr.2015.09.006 0169-409X/© 2012 Published by Elsevier B.V.
what concerns recent developments of vaginal drug delivery, Fernández-Romero et al. present a thorough review on methodologies and results of microbicide preclinical characterization (Preclinical assessments of vaginal microbicide candidate safety and efficacy). The second set of this issue is focused on general formulation strategies developed to improve efficacy, safety and compliance regarding vaginal drug delivery: Caramella et al. revise Mucoadhesive and thermogelling systems for vaginal drug delivery and their major recent developments applied to different dosage forms for a variety of applications, either for local or systemic drug delivery. Advanced drug delivery systems, particularly polymeric nanotechnologies are then presented by das Neves et al. (Polymer-based drug nanocarriers for vaginal drug delivery) highlighting their major pharmacokinetic advantages concerning interactions with fluids and vaginal tissues and their potential limitations. The third set of papers is focused in specific applications of vaginal formulations: Rodríguez-Gascón et al. revised the potentials of nucleic acid delivery systems (either viral or non-viral vectors), particularly concerning the prevention and treatment of sexually transmitted diseases (Vaginal gene therapy). Nader-Macías and Juárez Tomás (Profiles and technological requirements of urogenital probiotics), present the technological challenges required for probiotic development and the currently available clinical studies that support their interest regarding the urogenital ailments. In a broader perspective, Palmeira-de-Oliveira et al. expose recent strategies to treat the most common vaginal infections such as vaginal bacteriosis, vulvovaginal candidosis, aerobic vaginitis and trichomonosis (New strategies for local treatment of vaginal infections). Finally, Antimisiaris and Mourtas focused on microbicides dosage forms and clinical trials to bring an overview on recent advances on anti-HIV vaginal delivery systems development. Since acceptability of vaginal products arises as a main factor for patient adherence and consequent efficacy of vaginal formulations, particularly for preventive purposes, special attention on this topic has been given in a review by Woodsong and Holt (Acceptability and preferences for vaginal dosage forms intended for prevention of HIV or HIV and pregnancy) on acceptability issues that must be considered in early stages of development, particularly for anti-HIV and contraceptive products. This issue represents a state-of-art description on Vaginal Drug Delivery strategies, although not exhaustive. Ecologic interactions and regulation, immunologic modulation, and renewed use of traditional therapeutic agents may constitute the subject of further work.
Contents lists available at ScienceDirect
Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr
Editorial
Special issue on vaginal drug delivery Rita Palmeira de Oliveira a,b, José Martinez de Oliveira a,c, Carla Caramella d a
CICS-Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal Pharmacy Department, Centro Hospitalar Cova da Beira, Covilhã, Portugal c Child and Women's Health Department, Centro Hospitalar Cova da Beira, Covilhã, Portugal d Department of Drug Sciences, University of Pavia, Pavia, Italy b
Whereas in the past the vagina was considered to be a passive organ, being part of the female reproductive apparatus, nowadays its relevance as a functional organ is consensual, and its role under different aspects, from sexuality to homeostasis, is recognized. It is, so, natural, that vaginal drug delivery has evolved from an almost exclusive local form of therapy to a broader route of drug delivery to either treat or prevent diseases and to allow for controlled or enhanced drug absorption. All these new therapeutic possibilities do take advantage of the unique anatomical and physiological features of the female reproductive organ that results in a systemic delivery of drugs avoiding hepatic first pass effect and gastrointestinal interferences while assuring, in accordance with the chosen formulation, high and/or stable local concentrations and reduced, enhanced and/or controlled systemic absorption. Simultaneously, the large investment in research related to prevention of sexually transmitted diseases has brought new insights in understanding vaginal pharmacokinetics and pharmacodynamics in the context of the development of microbicides. This issue on Vaginal Drug Delivery aims to provide an overview of recent developments in this field either for local or systemic, therapeutic or preventive strategies. New technological approaches of traditionally unsolved limitations as well as new perspectives and potentials of the vaginal route are addressed. Performance issues are also discussed concerning vaginal formulations and in vitro, ex vivo and in vivo tests both for safety and efficacy assessments of vaginal products are reviewed. Finally, an important focus is given to consumer's opinions, through evaluating women's perspectives, preferences and adherence concerning vaginal dosage forms, particularly in the context of contraceptives and microbicides, since their consistent and correct use represents a main factor for efficacy and must be carefully considered for the development of successful vaginal products. Planned under a logical sequence, the first papers address the physiological basis of vaginal drug delivery and the methodologies for preclinical characterization of vaginal formulations. Katz et al. (Vaginal drug distribution modeling) explain the importance of drug distribution modeling in the vaginal environment as a tool to predict drug delivery to the vaginal lumen and drug transportation through the vaginal walls with a specific focus on dosage form determinants. In the second review, Machado et al. address the in vitro, ex vivo and in vivo methodologies used to study drug permeation through the vaginal walls (Studies and methodologies on vaginal drug permeation), and following, and due to the particular interest of microbicides design and characterization in
http://dx.doi.org/10.1016/j.addr.2015.09.006 0169-409X/© 2012 Published by Elsevier B.V.
what concerns recent developments of vaginal drug delivery, Fernández-Romero et al. present a thorough review on methodologies and results of microbicide preclinical characterization (Preclinical assessments of vaginal microbicide candidate safety and efficacy). The second set of this issue is focused on general formulation strategies developed to improve efficacy, safety and compliance regarding vaginal drug delivery: Caramella et al. revise Mucoadhesive and thermogelling systems for vaginal drug delivery and their major recent developments applied to different dosage forms for a variety of applications, either for local or systemic drug delivery. Advanced drug delivery systems, particularly polymeric nanotechnologies are then presented by das Neves et al. (Polymer-based drug nanocarriers for vaginal drug delivery) highlighting their major pharmacokinetic advantages concerning interactions with fluids and vaginal tissues and their potential limitations. The third set of papers is focused in specific applications of vaginal formulations: Rodríguez-Gascón et al. revised the potentials of nucleic acid delivery systems (either viral or non-viral vectors), particularly concerning the prevention and treatment of sexually transmitted diseases (Vaginal gene therapy). Nader-Macías and Juárez Tomás (Profiles and technological requirements of urogenital probiotics), present the technological challenges required for probiotic development and the currently available clinical studies that support their interest regarding the urogenital ailments. In a broader perspective, Palmeira-de-Oliveira et al. expose recent strategies to treat the most common vaginal infections such as vaginal bacteriosis, vulvovaginal candidosis, aerobic vaginitis and trichomonosis (New strategies for local treatment of vaginal infections). Finally, Antimisiaris and Mourtas focused on microbicides dosage forms and clinical trials to bring an overview on recent advances on anti-HIV vaginal delivery systems development. Since acceptability of vaginal products arises as a main factor for patient adherence and consequent efficacy of vaginal formulations, particularly for preventive purposes, special attention on this topic has been given in a review by Woodsong and Holt (Acceptability and preferences for vaginal dosage forms intended for prevention of HIV or HIV and pregnancy) on acceptability issues that must be considered in early stages of development, particularly for anti-HIV and contraceptive products. This issue represents a state-of-art description on Vaginal Drug Delivery strategies, although not exhaustive. Ecologic interactions and regulation, immunologic modulation, and renewed use of traditional therapeutic agents may constitute the subject of further work.
