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WIREs Nanomed Nanobiotechnol
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Overview of the blood compatibility of nanomedicines: A trend analysis of in vitro and in vivo studies

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As nanomedicines have the potential to address many currently unmet medical needs, the early identification of regulatory requirements that could hamper a smooth translation of nanomedicines from the laboratory environment to clinical applications is of utmost importance. The blood system is especially relevant as many nanomedicinal products that are currently under development are designed for intravenous administration and cells of the blood system will be among the first biological systems exposed to the injected nanomedicine. This review collects and summarizes the current knowledge related to the blood compatibility of nanomedicines and nanomaterials with a potential use in biomedical applications. Different types of nanomedicines were analyzed for their toxicity to the blood system, and the role of their physicochemical properties was further elucidated. Trends were identified related to: (a) the nature of the most frequently occurring blood incompatibilities such as thrombogenicity and complement activation, (b) the contribution of physicochemical properties to these blood incompatibilities, and (c) the similarities between data retrieved from in vivo and in vitro studies. Finally, we provide an overview of available standards that allow evaluating the compatibility of a material with the blood system. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Flow diagram of the methodology used to select articles which were included in the study. It is based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). The diagram maps out the number of records (n) identified, included, and excluded; and the reasons for exclusion
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Number of publications associating specific physicochemical properties of nanomedicines with each of the studied endpoints for blood toxicity in vitro: Hematology (a), coagulation (b), platelets (c), and complement activation (d)
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Number of publications associating specific physicochemical properties of nanomedicines with each of the studied endpoints for blood toxicity in vivo: Hematology (a), thrombosis (b), and complement activation (c)
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Number of identified publications associating key physicochemical properties of nanomedicines with general blood toxicities in vivo (left) and in vitro (right). Surface‐related properties were the most reported properties having an influence on blood adversities. The category Others includes properties such as shape, type of drug encapsulated, porosity, roughness, or elasticity
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Number of publications reporting blood toxicities in vitro for inorganic (a), polymer‐based (b) and lipid‐based NPs (c). Alterations on coagulation and platelets counted together were the main adversity for inorganic NPs in vitro. Polymer‐based NPs were the most compatible NPs. Complement activation was the most frequently reported blood toxicity associated with lipid‐based NPs
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Number of publications reporting blood adverse effects in vivo for inorganic (a), polymer‐based (b) and lipid‐based NPs (c). The main adversity associated with inorganic NPs in vivo was thrombosis. Polymers did not show relevant blood toxicities, and lipid‐based NPs were linked with undesired complement activation
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General blood incompatibilities linked to the different types of nanomedicines in vitro. Inorganic NPs were the type of nanomedicines most frequently associated with blood incompatibilities (a). The different types of nanomaterials included in each type (color—coded), and the number of publications found for each nanomaterial in vitro is shown. The highest number of publications were found for polymeric NPs (n = 123) (b)
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General blood incompatibilities linked to the types of nanomedicines in vivo. In all, 46 articles out of the 147 screened publications reported blood incompatibilities, and inorganic nanoparticles were most frequently associated with blood toxicities (a). Types of nanomedicines and nanomaterials with potential use in biomedicine retrieved from the screened publications (color—coded) and number of publications found for each type of nanomaterial. For inorganic NPs only one publication was found for some NPs, which were grouped under the category Other (inorganic) (b)
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Number of publications (n) reporting blood incompatibilities for nanomedicines, in vivo (a) or in vitro (b). The most frequently reported blood incompatibility in vivo was thrombosis. Alterations on coagulation and platelets are in vitro endpoints corresponding to thrombosis in vivo; counted together, they are also the main blood incompatibility in vitro
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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

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