21 research outputs found

    Emerging advances of nanotechnology in drug and vaccine delivery against viral associated respiratory infectious diseases (VARID)

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    Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

    Bioengineered tissue models for the development of dynamic immuno-associated tumor models and high-throughput immunotherapy cytotoxicity assays

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    Cancer immunotherapy is rapidly developing, with numerous therapies approved over the past decade and more therapies expected to gain approval in the future. However, immunotherapy of solid tumors has been less successful because immunosuppressive barriers limit immune cell trafficking and function against cancer cells. Interactions between suppressive immune cells, cytokines, and inhibitory factors are central to cancer immunotherapy approaches. In this review, we discuss recent advances in utilizing microfluidic platforms for understanding cancer-suppressive immune system interactions. Dendritic cell (DC)-mediated tumor models, infiltrated lymphocyte-mediated tumor models e.g., natural killer (NK) cells, T cells, chimeric antigen receptor (CAR) T cells, and macrophages, monocyte-mediated tumor models, and immune checkpoint blockade (ICB) tumor models are among the various bioengineered immune cell�cancer cell interactions that we reviewed herein. © 2020 This review is focused on introducing the role of bioengineering in-vitro models and particularly microfluidic tissue platforms in elucidating the underlying mechanisms of immune �tumor cells interactions in favor of more efficient immunotherapy interventions. © 202

    Formation of Tumor Spheroids by Spontaneous Cellular Aggregation in Incubation: Effect of Agarose as a Compaction Agent

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    Tumor spheroids is a 3D culture of cancer cells. This type of cell culture is a great tool for the evaluation of novel nanomedicine systems and in other areas of biomedical engineering. The main advantage over monolayer cell cultures is the biomimetic microenvironment which is appropriate for recapitulating tumor complexity. However, current tumor spheroids obtention methods require sophisticated and expensive equipment and are time-consuming. It is possible to obtain these tumor spheroids by centrifugation of the suspended cancer cells in round-bottom tubes and using compaction agents, for example agarose, which is a polysaccharide well known for its function of forming gels. Herein, we developed a method for obtaining cancer spheroids varying the centrifugation time and the concentration of agarose. The variation in spheroid size was analyzed. No significant changes were observed in the morphology or in the initial size and growth of the spheroids; except in those obtained with the shortest centrifugation time. The cell viability of spheroids that showed growth as a function of incubation time was evaluated. Viability greater than 80% was presented, however, the cell viability does not grow when the size of the spheroidal tumor increases. This simple and effective method for obtaining in vitro tumors represents a tool to further studies in Nanomedicine systems or the development of new anticancer drugs

    In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain

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    The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.This work was supported by the Alberta Prion Research Institute, Alberta Innovates BioSolutions, Natural Sciences and Engineering Research of Canada, NPRP9-144-3-021 from Qatar Foundation , GCC-2017-005 from GCC co-fund program, QUUG-CENG-MIE-15/16-7 and QUST-CENG-FALL-15/16-20 from Qatar University , the Farouk Jabre interdisciplinary research award from American University of Beirut , and the CNRS grant from National Council for Scientific Research , Lebanon, for the support for this paper.Scopu

    A Drug-Eluting Injectable NanoGel for Localized Delivery of Anticancer Drugs to Solid Tumors

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    Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements

    Emerging Advances of Nanotechnology in Drug and Vaccine Delivery against Viral Associated Respiratory Infectious Diseases (VARID)

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    Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines
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