Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part I. Effect of process variables on the mean size

PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA) were prepared by double emulsion solvent evaporation method. This Part I will focus on size and size distribution of prepared NPs, whereas encapsulation efficiency will be discussed in Part II. It was found that mean hydrodynamic particle size was influenced by five important process variables. To explore their effects, a five-factorial, three-level experimental design and statistical analysis were carried out using STATISTICA® software. Effect of process variables on the mean size of nanoparticles was investigated and finally conditions to minimize size of NPs were proposed. GAMS™/MINOS software was used for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to 329 nm depending on the process conditions. Smallest possible mean particle size can be achieved by using low polymer concentration and high dispersion energy (enough sonication time) along with small aqueous/organic volume ratio

Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: Inherent potential for biosynthetic versus live recombinant microbicides

<p>Abstract</p> <p>Background</p> <p>Herpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endunucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.</p> <p>Methods and Results</p> <p>Using the whole genome of HSV-2, 289 REases and the bioinformatics software Webcutter2; we searched for potential recognition sites by way of genome wide palindromics. REase application in HSV-2 biomedical therapy was modeled concomitantly. Of the 289 enzymes analyzed; 77(26.6%) had potential to cleave the HSV-2 genome in > 100 but < 400 sites; 69(23.9%) in > 400 but < 700 sites; and the 9(3.1%) enzymes: BmyI, Bsp1286I, Bst2UI, BstNI, BstOI, EcoRII, HgaI, MvaI, and SduI cleaved in more than 700 sites. But for the 4: PacI, PmeI, SmiI, SwaI that had no sign of activity on HSV-2 genomic DNA, all 130(45%) other enzymes cleaved < 100 times. In silico palindromics has a PPV of 99.5% for in situ REase activity (2) Two models detailing how the REase EcoRII may be applied in developing interventions against HSV-2 are presented: a nanoparticle for microbicide development and a "recombinant lactobacillus" expressing cell wall anchored receptor (truncated nectin-1) for HSV-2 plus EcoRII.</p> <p>Conclusion</p> <p>Viral genome slicing by way of these bacterially- derived R-M enzymatic peptides may have therapeutic potential in HSV-2 infection; a cofactor for HIV-1 acquisition and transmission.</p

Linking Oviposition Site Choice to Offspring Fitness in Aedes aegypti: Consequences for Targeted Larval Control of Dengue Vectors

Controlling the mosquito Aedes aegypti, the predominant dengue vector, requires understanding the ecological and behavioral factors that influence population abundance. Females of several mosquito species are able to identify high-quality egg-laying sites, resulting in enhanced offspring development and survival, and ultimately promoting population growth. Here, the authors investigated egg-laying decisions of Ae. aegypti. Paradoxically, they found that larval survival and development were poorest in the containers females most often selected for egg deposition. Thus, egg-laying decisions may contribute to crowding of larvae and play a role in regulating mosquito populations. The authors also tested whether removal of the containers producing the most adult mosquitoes, a World Health Organization-recommended dengue prevention strategy, changes the pattern of how females allocate their eggs. Elimination of the most productive containers led to a more even distribution of eggs in one trial, but not another. These results suggest that behavioral adjustments by egg-laying females may lessen the effectiveness of a common mosquito control tactic. The authors advocate incorporating control strategies that take advantage of the natural egg-laying preferences of this vector species, such as luring egg-laying females to traps or places where their eggs will accumulate, but not develop

Controllable Microfluidic Production of Drug-Loaded PLGA Nanoparticles Using Partially Water-Miscible Mixed Solvent Microdroplets as a Precursor

We present a versatile continuous microfluidic flow-focusing method for the production of Doxorubicin (DOX) or Tamoxifen (TAM)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). We use a partially water-miscible solvent mixture (dimethyl sulfoxide DMSO + dichloromethane DCM) as precursor drug/polymer solution for NPs nucleation. We extrude this partially water-miscible solution into an aqueous medium and synthesized uniform PLGA NPs with higher drug loading ability and longer sustained-release ability than conventional microfluidic or batch preparation methods. The size of NPs could be precisely tuned by changing the flow rate ratios, polymer concentration, and volume ratio of DCM to DMSO (VDCM/VDMSO) in the precursor emulsion. We investigated the mechanism of the formation of NPs and the effect of VDCM/VDMSO on drug release kinetics. Our work suggests that this original, rapid, facile, efficient and low-cost method is a promising technology for high throughput NP fabrication. For the two tested drugs, one hydrophilic (Doxorubicin) the other one hydrophobic (Tamoxifen), encapsulation efficiency (EE) as high as 88% and mass loading content (LC) higher than 25% were achieved. This new process could be extended as an efficient and large scale NP production method to benefit to fields like controlled drug release and nanomedicine.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de Glioblastom