Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women

Madan, Rebecca Pellett; Dezzutti, Charlene S.; Rabe, Lorna K.; Hillier, Sharon L.; Marrazzo, Jeanne M.; McGowan, Ian; Richardson, Barbra A.; Herold, Betsy C.

doi:10.1111/aji.12412

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…In particular, a dendrimer-based drug Vivagel ® preventing the HIV infection has been approved for using in condom lubricants [ 96 , 97 ]. It has also been subjected to clinical trials in the bacterial vaginosis treatment [ 98 , 99 ]. These recent positive findings stimulate the development of new dendrimer-based constructions for future medicine.…”

Section: Complexes and Conjugates Of Proteins And Peptides With Dementioning

confidence: 99%

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

2019

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Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future.

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Section: Complexes and Conjugates Of Proteins And Peptides With Dementioning

confidence: 99%

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

2019

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“… 6–9 Inflammatory processes can recruit HIV-infected or target cells to the genitalia, thereby increasing risks of both transmission and acquisition. Studies of inflammatory markers confirm that cells are associated with high viral loads (VL) in cervico-vaginal fluids, 10 and cytokine markers 11–14 and innate antimicrobial responses 15 , 16 are linked to HIV acquisition. Causes of these inflammatory processes warrant closer investigation.…”

Section: Introductionmentioning

confidence: 99%

Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994–2012

Wall

Kilembe

Vwalika

et al. 2017

International Journal of Epidemiology

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BackgroundStudies have demonstrated the role of ulcerative and non-ulcerative sexually transmitted infections (STI) in HIV transmission/acquisition risk; less is understood about the role of non-specific inflammatory genital abnormalities.MethodsHIV-discordant heterosexual Zambian couples were enrolled into longitudinal follow-up (1994–2012). Multivariable models estimated the effect of genital ulcers and inflammation in both partners on time-to-HIV transmission within the couple. Population-attributable fractions (PAFs) were calculated.ResultsA total of 207 linked infections in women occurred over 2756 couple-years (7.5/100 CY) and 171 in men over 3216 CY (5.3/100 CY). Incident HIV among women was associated with a woman’s non-STI genital inflammation (adjusted hazard ratio (aHR) = 1.55; PAF = 8%), bilateral inguinal adenopathy (BIA; aHR = 2.33; PAF = 8%), genital ulceration (aHR = 2.08; PAF = 7%) and the man’s STI genital inflammation (aHR = 3.33; PAF = 5%), BIA (aHR = 3.35; PAF = 33%) and genital ulceration (aHR = 1.49; PAF = 9%). Infection among men was associated with a man’s BIA (aHR = 4.11; PAF = 22%) and genital ulceration (aHR = 3.44; PAF = 15%) as well as with the woman’s non-STI genital inflammation (aHR = 1.92; PAF = 13%) and BIA (aHR = 2.76; PAF = 14%). In HIV-M+F- couples, the man being uncircumcised. with foreskin smegma. was associated with the woman’s seroconversion (aHR = 3.16) relative to being circumcised. In F+M- couples, uncircumcised men with BIA had an increased hazard of seroconversion (aHR = 13.03 with smegma and 4.95 without) relative to being circumcised. Self-reporting of symptoms was low for ulcerative and non-ulcerative STIs.ConclusionsOur findings confirm the role of STIs and highlight the contribution of non-specific genital inflammation to both male-to-female and female-to-male HIV transmission/acquisition risk. Studies are needed to characterize pathogenesis of non-specific inflammation including inguinal adenopathy. A better understanding of genital practices could inform interventions.

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“…Recently, one dendrimer-containing gel drug, Vivagel ® , has been approved by the US FDA for the use in condom lubricants to prevent the HIV infection [ 8 , 9 ]. It is subjected for clinical trials as a therapeutic to treat bacterial vaginosis as well [ 10 , 11 ]. This recent success encourages the development of new dendrimer-containing constructions and materials for innovative medicine.…”

Section: Introductionmentioning

confidence: 99%

Hydrogels of Polycationic Acetohydrazone-Modified Phosphorus Dendrimers for Biomedical Applications: Gelation Studies and Nucleic Acid Loading

et al. 2018

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In this work, we report the assemblage of hydrogels from phosphorus dendrimers in the presence of biocompatible additives and the study of their interactions with nucleic acids. As precursors for hydrogels, phosphorus dendrimers of generations 1–3 based on the cyclotriphosphazene core and bearing ammonium or pyridinium acetohydrazones (Girard reagents) on the periphery have been synthesized. The gelation was done by the incubation of dendrimer solutions in water or phosphate-buffered saline in the presence of biocompatible additives (glucose, glycine or polyethylene glycol) to form physical gels. Physical properties of gels have been shown to depend on the gelation conditions. Transmission electron microscopy revealed structural units and well-developed network structures of the hydrogels. The hydrogels were shown to bind nucleic acids efficiently. In summary, hydrogels of phosphorus dendrimers represent a useful tool for biomedical applications.

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Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women

Cited by 14 publications

References 43 publications

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994–2012

Hydrogels of Polycationic Acetohydrazone-Modified Phosphorus Dendrimers for Biomedical Applications: Gelation Studies and Nucleic Acid Loading

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