Examinando por Autor "Farokhzad, Omid C."

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    A solvent-free thermosponge nanoparticle platform for efficient delivery of labile proteins
    (Nano Letters, 2014-11) Choi, Won Ila; Kamaly, Nazilaa; Riol-Blanco, Lorenab; Lee, In-Hyuna; Wu, Juna; Swami, Archanaa; Vilos, Cristiana, c; Yameen, Basita; Yu, Mikyunga; Shi, Jinjuna; Tabas, Irad, e, f; Von Andrian, Ulrich H.; Jon, Sangyongg; Farokhzad, Omid C.
    Protein therapeutics have gained attention recently for treatment of a myriad of human diseases due to their high potency and unique mechanisms of action. We present the development of a novel polymeric thermosponge nanoparticle for efficient delivery of labile proteins using a solvent-free polymer thermo-expansion mechanism with clinical potential, capable of effectively delivering a range of therapeutic proteins in a sustained manner with no loss of bioactivity, with improved biological half-lives and efficacy in vivo. © 2014 American Chemical Society.
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    Insight into nanoparticle cellular uptake and intracellular targeting
    (2014) Yameen, Basit; Choi, Won Il; Vilos, Cristian; Swami, Archana; Shi, Jinjun; Farokhzad, Omid C.
    Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for efficient cellular uptake through the plasma membrane and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. Cellular internalization routes determine the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine and presents an account of ligand-targeted nanoparticles for receptor-mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand-targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has already resulted in remarkable progress towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial barrier. A detailed overview of the recent developments in subcellular targeting as a novel platform for next-generation organelle-specific nanomedicines is also provided. Each section of the review includes prospects, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations. © 2014 Elsevier B.V. All rights reserved.
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    Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis
    (American Chemical Society, 2016-05) Kamaly, Nazila; Fredman, Gabrielle; Fojas, Jhalique Jane R.; Subramanian, Manikandan; Choi, Won Iia; Zepeda, Katherinea; Vilos, Cristiana; Yu, Mikyunga; Gadde, Suresha; Wu, Juna; Milton, Jaclyna; Carvalho, Leitao; Fernandes, Livia; Hasan, Moaraja; Gao, Huayia; Nguyen, Vance; Harris, Jordana; Tabas, Ira; Farokhzad, Omid C.
    Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr-/- mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis. © 2016 American Chemical Society.