Nanoparticles for treatment of posterior segment ocular diseases and conditions

The present invention concerns nanoparticles useful for treating posterior segment ocular diseases or conditions, such as macular degeneration and diabetic retinopathy; compositions comprising the nanoparticles; methods for producing the nanoparticles; and methods for treating posterior segment ocular diseases or conditions, comprising administering the nanoparticles or compositions to the ocular posterior segment of an afflicted eye

Nanoparticles for treatment of posterior segment ocular diseases and conditions

The present invention concerns nanoparticles useful for treating posterior segment ocular diseases or conditions, such as macular degeneration and diabetic retinopathy; compositions comprising the nanoparticles; methods for producing the nanoparticles; and methods for treating posterior segment ocular diseases or conditions, comprising administering the nanoparticles or compositions to the ocular posterior segment of an afflicted eye

Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In Vitro Model: A Preliminary Report

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the United States, affecting approximately 11 million patients. AMD is caused primarily by an upregulation of vascular endothelial growth factor (VEGF). In recent years, aflibercept injections have been used to combat VEGF. However, this treatment requires frequent intravitreal injections, leading to low patient compliance and several adverse side effects including scarring, increased intraocular pressure, and retinal detachment. Polymeric nanoparticles have demonstrated the ability to deliver a sustained release of drug, thereby reducing the necessary injection frequency. Aflibercept (AFL) was encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) via double emulsion diffusion. Scanning electron microscopy showed the NPs were spherical and dynamic light scattering demonstrated that they were uniformly distributed (PDI \u3c 1). The encapsulation efficiency and drug loading were 75.76% and 7.76% respectively. In vitro release studies showed a sustained release of drug; 75% of drug was released by the NPs in seven days compared to the full payload released in 24 h by the AFL solution. Future ocular in vivo studies are needed to confirm the biological effects of the NPs. Preliminary studies of the proposed aflibercept NPs demonstrated high encapsulation efficiency, a sustained drug release profile, and ideal physical characteristics for AMD treatment. This drug delivery system is an excellent candidate for further characterization using an ocular neovascularization in vivo model

Nano-drug delivery platform for glucocorticoid use in skeletal muscle injury.

Glucocorticoids are utilized for its anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback with use of glucocorticoids is that it leads to senescence and toxicity. Therefore, based on the idea that decreasing particle size allows for increased surface area and bio-availability of the drug, in the present study we hypothesized that nano-delivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone loaded PLGA (poly lactic-co-glycolic acid) nanoparticles were prepared using nanoprecipitation method. The morphological characteristics of the nanoparticles were studied under scanning electron microscope. The particle size of nanoparticles was 217.5±19.99 nm with polydispersity index (PDI) of 0.14±0.07. The nanoparticles encapsulation efficiency was 34.57±1.99% with in vitro drug release profile exhibiting a sustained release pattern over 10 days. We identified improved skeletal muscle myoblast performance with improved closure of the wound along with increased cell viability at 10nM nano-Dexamethasone-PLGA, however dexamethasone solution (1µM) was injurious to cells since the migration efficiency was decreased. In addition, the use of NP-Dexamethasone decreased LPS induced LDH release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nano-particles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Environmental aspects of RIGHTRAC TDP- green munitions

The Defense Research and Development Canada (DRDC, Valcartier, QC) is developing new green explosive and propellant formulations, as part of a sustainable training strategy for the Canadian Army. The present research responds to the needs of DRDC by providing necessary physicochemical, chemical, and ecotoxicological data to help understand the environmental transport, fate and impact of new formulations developed within the RIGHTTRAC (Revolutionary Insensitive, Green and Healthier Training Technology with Reduced Adverse Contamination) project. The present study summarizes the dissolution, transport, transformation, and ecotoxicity of three propellant formulations, SP 7993, SP Unique, and CMR170, and their soluble components, NG, DPA, ATEC, MC, and EC. In addition, it gathers ecotoxicity data for an explosive formulation, GIM, which has been aged for periods varying from 6 to 24 months. Amongst the three propellant formulations tested, the single base formulation SP 7993 was found to be the most stable in terms of dissolution, even more stable than the formulation New Green M1 identified as the most stable of previously studied formulations. If scattered on soil surface and subjected to precipitations SP 7993 will give rise to low leakage of ATEC and the latter will not persist in soil. When comparing the two double base formulations, CRM170 appeared to be more stable than SP Unique. Although the MC/graphite coating present in CMR170 might have been responsible for the higher stability this could not be ascertained due to the concomitant higher NC content of CMR170, which also decreased its ability to dissolve.Afin de d\ue9velopper des armes moins nocives pour l\u2019environnement, l\u2019arm\ue9e canadienne \ue9tudie pr\ue9sentement la possible utilisation de nouvelles formulations d\u2019explosifs ou de charge propulsive. La pr\ue9sente \ue9tude r\ue9pond ainsi aux besoins de RDDC, Valcartier, QC, et vise \ue0 produire des donn\ue9es physiques, chimiques et \ue9cotoxicologiques n\ue9cessaires pour pr\ue9dire le sort et l\u2019impact de nouvelles formulations d\ue9velopp\ue9es dans le cadre du projet RIGHTTRAC (Revolutionary Insensitive, Green and Healthier Training Technology with Reduced Adverse Contamination). La pr\ue9sente \ue9tude r\ue9sume la dissolution, le transport, la transformation et l\u2019\ue9cotoxicit\ue9 de trois formulations de charge propulsive, SP 7993, SP Unique, et CMR170, ainsi que de leurs constituants, NG, DPA, ATEC, MC et EC. De plus, elle r\ue9sume aussi l\u2019\ue9cotoxicit\ue9 d\u2019une formulation d\u2019explosifs, GIM, vieillie durant des p\ue9riodes variant de 6 \ue0 24 mois. Parmi les trois formulations test\ue9es, SP 7993 s\u2019est av\ue9r\ue9e \ueatre la plus stable en terme de dissolution, plus stable m\ueame que la formulation New Green M1 pr\ue9c\ue9demment identifi\ue9e comme tr\ue8s stable. Si des particules de SP 7993 dispers\ue9es \ue0 la surface du sol sont sujettes \ue0 des pr\ue9cipitations elles devraient donner lieu \ue0 une dispersion minime d\u2019ATEC. Ce dernier devrait rapidement dispara\ueetre \ue9tant donn\ue9e sa faible stabilit\ue9 dans les sols.NRC publication: Ye

Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice

The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner