Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 157, Issue -, Pages 83-95Publisher
ELSEVIER
DOI: 10.1016/j.addr.2020.04.012
Keywords
Adjuvanticity; Adverse reactions; Complement inhibitors; Complement system; Complosome; Opsonization; Polymers; Protein adsorption
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Funding
- Danish Agency for Science, Technology and Innovation [09-065746]
- Lundbeckfonden [R100-A9443]
- European Commission [310337, 212043]
- NIH [R01 EB022040]
- European Commission FP7 (University of Padova)
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Considering the multifaceted protective and homeostatic roles of the complement system, many consequences arise when drug carriers, and particulate pharmaceutical formulations clash with complement proteins, and trigger complement cascade. Complement activation may induce formulation destabilization, promote opsonization, and affect biological and therapeutic performance of pharmaceutical nano- and micro-particles. In some cases, complement activation is beneficial, where complement may play a role in prophylactic protection, whereas uncontrolled complement activation is deleterious, and contributes to disease progression. Accordingly, design initiatives with particulate medicines should consider complement activation properties of the end formulation within the context of administration route, dosing, systems biology, and therapeutic perspective. Here we examine current progress in mechanistic processes underlying complement activation by pre-clinical and clinical particles, identify opportunities and challenges ahead, and suggest future directions in nanomedicine-complement interface research. (C) 2020 Elsevier B.V. All rights reserved.
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