UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C.

Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor.

Biomedical applications of biodegradable polycaprolactone-functionalized magnetic iron oxides nanoparticles and their polymer nanocomposites.

Magnetic nanoparticles (MNPs) have gained significant attention among several nanoscale materials during the last decade due to their unique properties. These properties make them successful nanofillers for drug delivery and a number of new biomedical applications. MNPs are more useful when combined with biodegradable polymers. In this review, we discussed the synthesis of polycaprolactones (PCL) and the various methods of synthesizing magnetic iron oxide nanoparticles. Then, the synthesis of composites that is made of PCL and magnetic materials (with special focus on iron oxide nanoparticles) were highlighted. In addition, we comprehensively reviewed their application in drug delivery, cancer treatment, wound healing, hyperthermia, and bone tissue engineering. Other biomedical applications of the magnetic PCL such as mitochondria targeting are highlighted. Moreover, biomedical applications of magnetic nanoparticles incorporated into other synthetic polymers apart from PCL are also discussed. Thus, great progress and better outcome with functionalized MNPs enhanced with polycaprolactone has been recorded with the biomedical applications of drug delivery and recovery of bone tissues.

Progress and Perspectives on HIV-1 microbicide development.

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.