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Prevention strategies play a key role in the fight against HIV/AIDS. Vaginal and rectal microbicides hold great promise in tackling sexual transmission of HIV-1, but effective and safe products are yet to be approved and made available to those in need. While most efforts have been placed in finding and testing suitable active drug candidates to be used in microbicide development, the last decade also saw considerable advances in the design of adequate carrier systems and formulations that could lead to products presenting enhanced performance in protecting from infection. One strategy demonstrating great potential encompasses the use of nanosystems, either with intrinsic antiviral activity or acting as carriers for promising microbicide drug candidates. Polymeric nanoparticles, in particular, have been shown to be able to enhance mucosal distribution and retention of promising antiretroviral compounds. One important aspect in the development of nanotechnology-based microbicides relates to the design of pharmaceutical vehicles that allow not only convenient vaginal and/or rectal administration, but also preserve or even enhance the performance of nanosystems. In this manuscript, we revise relevant work concerning the selection of vaginal/rectal dosage forms and vehicle formulation development for the administration of microbicide nanosystems. We also pinpoint major gaps in the field and provide pertinent hints for future work.

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Bacteria are able to colonize and thrive in a variety of different environments as a biofilm, but only within the last half century new insights have been gained in this complex biosystem. Bacterial biofilms play a major role in human health by forming a defensive barrier against antibacterial chemical therapeutics and other potential pathogens, and in infectious disease when the bacteria invade normally sterile compartments. Quorum sensing is the signaling network for cell-to-cell communication and utilized by bacteria to regulate biofilms and other cellular processes. This review will describe recent advances in quorum sensing and biofilms. Initially, it will focus on Streptococcus pneumoniae biofilm regulation and the involvement of the ComABCDE pathway. As part of this review an original analysis of the genotypic and phenotypic variation of the signaling molecule, ComC and its cognate receptor ComD, firstly within the pneumococcal species and then within the genus Streptococcus will be presented. Additionally, a pathway similar to ComABCDE, the BlpABCSRH that regulates bacteriocin and immunity protein production that inhibit the growth of competing bacteria will be described. This review will then examine a third quorum sensing mechanism in the pneumococcus, the LuxS/AI-2, and present a novel gene and protein sequence comparative analysis that indicates its occurrence is more universal across bacterial genera compared with the Com pathway, with more sequence similarities between bacterial genera that are known to colonize the mucosal epithelium.

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