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Critical Reviews in Biotechnology Nov 2019The prevention of infectious diseases is a global challenge where multidrug-resistant bacteria or "superbugs" pose a serious threat to worldwide public health.... (Review)
Review
The prevention of infectious diseases is a global challenge where multidrug-resistant bacteria or "superbugs" pose a serious threat to worldwide public health. Microtopographic surfaces have attracted much attention as they represent a biomimetic and nontoxic surface antibacterial strategy to replace biocides. The antimicrobial effect of such natural and biomimetic surface nanostructures involves a physical approach which eradicates bacteria via the structural features of the surfaces without any release of biocides or chemicals. These recent developments present a significant proof-of-concept and a powerful tool in which cellular adhesion and death caused by a physical approach, can be controlled by the micro/nanotopology of such surfaces. This represents an innovative direction of development of clean, effective and nonresistant antimicrobial surfaces. The minireview will cover novel approaches for the construction of nanostructures on surfaces in order to create antimicrobial surface in an environmentally friendly, nontoxic manner.
Topics: Animals; Anti-Infective Agents; Humans; Nanostructures; Surface Properties
PubMed: 31331202
DOI: 10.1080/07388551.2019.1641788 -
Journal of the International AIDS... Apr 2013After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women... (Review)
Review
After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1) Adherence measurement in clinical trials, (2) Comprehension of use instructions/Instructions for use, (3) Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4) Partner influence on use, (5) Retention and continuation and (6) Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.
Topics: Administration, Intravaginal; Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Male; Medication Adherence
PubMed: 23561044
DOI: 10.7448/IAS.16.1.18505 -
Clinical Pharmacology and Therapeutics Dec 2018Efforts in developing an effective vaccine for human immunodeficiency virus (HIV) has been challenging as HIV strains are highly variable and exhibit extraordinary... (Review)
Review
Efforts in developing an effective vaccine for human immunodeficiency virus (HIV) has been challenging as HIV strains are highly variable and exhibit extraordinary mutability. Despite condom usage and pre-exposure prophylaxis as excellent prevention strategies, lack of accessibility in some developing countries and low adherence due to sociocultural factors continue to act as barriers in reducing the HIV epidemic. Microbicides are topical therapies developed to prevent HIV and other sexually transmitted infections during intercourse. Microbicides applied vaginally or rectally are intended to prevent HIV infection at the site of transmission by either inhibiting its entry into immune cells or prevent viral replication. This review will summarize some of the current state-of-the-art microbicide formulations that are in preclinical and clinical stages of development and discuss some of the challenges associated with microbicide development.
Topics: Administration, Intravaginal; Administration, Rectal; Animals; Anti-HIV Agents; Anti-Infective Agents, Local; Dosage Forms; Drug Development; Female; HIV; HIV Infections; Host-Pathogen Interactions; Humans; Male; Treatment Outcome
PubMed: 30107032
DOI: 10.1002/cpt.1212 -
Drug Delivery and Translational Research Dec 2017Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e.,... (Review)
Review
Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production, and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.
Topics: Administration, Rectal; Administration, Topical; Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Male; Patient Compliance; Patient Preference; Sexual Behavior; Vaginal Creams, Foams, and Jellies
PubMed: 28589452
DOI: 10.1007/s13346-017-0385-4 -
Social Science & Medicine (1982) Jan 2005With growing recognition of the potential value of microbicides for HIV/STI prevention, the importance of the acceptability of this brand-new technology has been widely... (Review)
Review
With growing recognition of the potential value of microbicides for HIV/STI prevention, the importance of the acceptability of this brand-new technology has been widely acknowledged. We review the current body of microbicide acceptability research, characterize the limitations in assessment approaches, and suggest strategies for improvement. Electronic databases and abstracts of recent meetings were searched for acceptability data regarding vaginal and rectal products that may be used for HIV prevention. Of the 61 studies reviewed, more than half assessed acceptability based primarily on the description of a hypothetical microbicide, or with the demonstration of a spermicide or lubricant. Physical characteristics of microbicidal products, their effects after insertion, and their effects on sensation during intercourse (for both partners) were the dimensions most frequently assessed (measured in 77%, 49% and 49% of studies, respectively). Attention to the social context of use was inadequate. As acceptability is likely to be a key determinant in the use-effectiveness of microbicides, in-depth understanding of the social processes that shape microbicide acceptability across diverse populations will become increasingly valuable. This includes exploring the effects that sexual partners, health care providers, and key opinion leaders have on the acceptability of microbicides among women and men, including youth and people living with HIV. Future research will benefit from studies of the acceptability of other contraceptive-barrier methods (especially the female condom), use of an agreed-upon operationalization of acceptability, use of acceptability assessments within clinical trials, expansion of measurement domains, and assessment of changes in perceptions of acceptability and use over time. Failure to understand the key factors associated with microbicide acceptability is likely to hinder the adoption and continued use of products that are effective in preventing HIV infection.
Topics: Anti-Infective Agents, Local; Condoms, Female; Consumer Behavior; Contraception Behavior; Decision Making; HIV Infections; Health Services Research; Humans; Sex Factors; Spermatocidal Agents
PubMed: 15522488
DOI: 10.1016/j.socscimed.2004.05.011 -
Current HIV Research Jan 2012Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the... (Review)
Review
Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development.
Topics: Administration, Topical; Anti-Infective Agents, Local; Anti-Retroviral Agents; Clinical Trials as Topic; Drug Evaluation, Preclinical; HIV Infections; Humans; Surface-Active Agents
PubMed: 22264041
DOI: 10.2174/157016212799304625 -
Current HIV Research Jan 2012There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the... (Review)
Review
There have been encouraging recent successes in the development of safe and effective topical microbicides to prevent vaginal or rectal HIV-1 transmission, based on the use of anti-retroviral drugs. However, much work remains to be accomplished before a microbicide becomes a standard element of prevention science strategies. Animal models should continue to play an important role in pre-clinical testing, with emphasis on safety, pharmacokinetic and efficacy testing.
Topics: Administration, Topical; Animals; Anti-Infective Agents, Local; Anti-Retroviral Agents; Disease Models, Animal; Drug Evaluation, Preclinical; HIV Infections; HIV-1; Macaca mulatta; Mice; Rabbits; Rats
PubMed: 22264049
DOI: 10.2174/157016212799304715 -
Virology Oct 2016The majority of HIV-1 infections occur via sexual intercourse. Women are the most affected by the epidemic, particularly in developing countries, due to their... (Review)
Review
The majority of HIV-1 infections occur via sexual intercourse. Women are the most affected by the epidemic, particularly in developing countries, due to their socio-economic dependence on men and the fact that they are often victims of gender based sexual violence. Despite significant efforts that resulted in the reduction of infection rates in some countries, there is still need for effective prevention methods against the virus. One of these methods for preventing sexual transmission in women is the use of microbicides. In this review we provide a summary of the progress made toward the discovery of affordable and effective HIV-1 microbicides and suggest future directions. We show that there is a wide range of compounds that have been proposed as potential microbicides. Although most of them have so far failed to show protection in humans, there are many promising ones currently in pre-clinical studies and in clinical trials.
Topics: Animals; Anti-Infective Agents; Drug Carriers; Drug Delivery Systems; Drug Discovery; Female; Genitalia, Female; HIV Infections; HIV-1; Humans; Male; Mucous Membrane; Sexually Transmitted Diseases, Viral
PubMed: 27429040
DOI: 10.1016/j.virol.2016.07.004 -
Advanced Drug Delivery Reviews Aug 2016Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following... (Review)
Review
Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called 'HIV microbicide' compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years.
Topics: Anti-Infective Agents; Contraceptive Devices, Female; Female; HIV Infections; Humans
PubMed: 26829289
DOI: 10.1016/j.addr.2016.01.015 -
Antiviral Research Dec 2010The clinical evaluation of microbicide formulations presents variable and interacting challenges. Specific domains of acceptability, pharmacokinetics, and toxicity... (Review)
Review
The clinical evaluation of microbicide formulations presents variable and interacting challenges. Specific domains of acceptability, pharmacokinetics, and toxicity interact with each other to potentially inhibit or enhance a microbicide's efficacy. Each of these is further influenced by application and use parameters in the relative presence (or absence) of vaginal and/or seminal fluids, ultimately impacting effectiveness. Historically, acceptability of formulation and use parameters, and their concomitant behavioral influences, have been considered separately from pharmacokinetics and toxicity. While independent evaluation of these elements is necessary in some respects, we must acknowledge that this approach is not sufficient for the successful development of microbicides. Each needs to be considered in an integrated clinical evaluation strategy. This article presents the rationale for such an approach. This article forms part of a special supplement covering two presentations on clinical evaluation of microbicides from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA.
Topics: Administration, Intravaginal; Anti-HIV Agents; Anti-Infective Agents, Local; Chemistry, Pharmaceutical; Clinical Trials as Topic; Dosage Forms; Drug Interactions; Drug and Narcotic Control; Female; HIV; HIV Infections; Host-Pathogen Interactions; Humans; Male; Sexual Behavior; Vagina
PubMed: 21109067
DOI: 10.1016/j.antiviral.2010.09.008