Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.
For advanced treatment of diseases such as cancer, multi component, multi functional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic co glycolic) acid (PLGA) polymer is formulated into a polymer lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.
Surface free energy (SFE) is a property resulted from the chemical structure and the orientation of the molecules at the surface boundary of the materials. For solids, it can be calculated from the contact angles of liquid drops with known surface tension, formed on the solid surface. There are various SFE evaluation methods based on different theoretical assumptions. In this study, SFE and the dispersive, polar, acidic and basic components of the SFE of a polymeric material, poly(methyl methacrylate) (PMMA), were calculated by using Zisman, Saito, Fowkes, Berthelot, Geometric mean, Harmonic mean, and Acid-base approaches. The results obtained from various liquid couples or triplets were compared.
The surface of a material is the most important part determining the acceptance by and compatibility with the environment. In many cases, although the bulk properties are excellent for a specific application, the surface may require to be modified and engineered in the desired direction. This is especially important for materials used in biological media, since the surface charge, hydophilicity and wettability are important for thrombosis formation, cell attachment or cell proliferation. In this study, poly(methyl methacrylate) films were prepared by solvent casting and their surfaces were modified by oxygen plasma treatment by applying powers of 20, 100 and 300 W. The effects of surface chemistry alterations on hydophilicity, work of adhesion, surface free energy and cell adhesion were examined. Cell attachment and proliferation are especially important for the materials used for tissue-engineering purposes. The results demonstrated that there is an optimum value for hydrophilicity and surface free energy which enhance cell attachment.
For any biomaterial placed into a biological medium, the surface properties of the material, such as porosity, crystallinity, presence and distribution of electrical charge and functional groups are very critical parameters that determine the acceptance or rejection of the material. Applications, especially tissue engineering require some surface modifications at the molecular level without disturbing the bulk properties of the implants in order to enhance the cell attachment on the material. An appropriate technique is the application of glow discharge plasma which employs no solvents, takes place at ambient temperatures, and alterations take place only at the surface by changing the surface chemistry along with surface free energy (SFE) and efficiency for cell-material interaction. In this study, poly(methyl methacrylate) (PMMA) film surfaces were modified with oxygen plasma. SFE and its dispersive and polar (acidic-basic) components of the modified surfaces were calculated by means of several theoretical approaches including geometric mean, harmonic mean and acid-base equations. The relation between SFE and its dispersive and polar components and cell attachment on surfaces were studied. The highest 3T3 cell attachment was obtained for the surface with the total SFE of 61.77 mJ/m 2 and polar component of 50.91 mJ/m 2 according to Geometric mean. The total SFE of this surface was calculated to be 61.06 mJ/m 2 and the polar component as 40.96 mJ/m 2 using the Harmonic mean method.
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