Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

Szebeni, János; Storm, Gert

doi:10.1016/j.bbrc.2015.06.177

Cited by 85 publications

(74 citation statements)

References 65 publications

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“…For example, nanosized micellar excipient Cremophor EL is known to cause complement activation, which is responsible for the hypersensitivity reaction to Cremophor EL–formulated paclitaxel (Taxol) [76, 77]. Likewise, complement activation–related pseudoallergy (CARPA) is the known undesirable side effect of the PEGylated liposomal doxorubicin formulation Doxil [78]. For these reasons, the inclusion of Taxol, Cremophor-EL, or Doxil into the in vitro complement activation assay serves as an internal nanoformulation-relevant positive control.…”

Section: Challenges and Considerationsmentioning

confidence: 99%

Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy

Dobrovolskaia

2015

Journal of Controlled Release

166

126

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Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany preclinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly complex. An understanding of both the immune compatibility of nanoformulations and their effects on hematological parameters is now recognized as an important step in the (pre)clinical development of nanomedicines. An evaluation of nanoparticle immunotoxicity is usually performed as a part of a traditional toxicological assessment; however, it often requires additional in vitro and in vivo specialized immuno- and hematotoxicity tests. Herein, I review literature examples and share the experience with the NCI Nanotechnology Characterization Laboratory assay cascade used in the early (discovery-level) phase of pre-clinical development to summarize common challenges in the immunotoxicological assessment of nanomaterials, highlight considerations and discuss solutions to overcome problems that commonly slow or halt the translation of nanoparticleformulated drugs toward clinical trials. Special attention will be paid to the grandchallenge related to detection, quantification and removal of endotoxin from nanoformulations, and practical considerations related to this challenge.

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Section: Challenges and Considerationsmentioning

confidence: 99%

Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy

Dobrovolskaia

2015

Journal of Controlled Release

166

126

View full text Add to dashboard Cite

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“…Moreover, the synthetic nature of these DDS may result in adverse immunogenic responses, such as the complement activation-related pseudoallergy (CARPA) effect upon liposomal administration, or unwanted accumulation in organs such as liver or kidneys. 6 Lastly, several of these synthetic nanoparticles have poor in vivo circulation time due to recognition by the body's immune system and premature elimination.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach for anti-tumor therapy

Goh

Lee

Zou

et al. 2017

IJN

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Cell-derived nanovesicles (CDNs) are an emerging class of biological drug delivery systems (DDS) that retain the characteristics of the cells they were derived from, without the need for further surface functionalization. CDNs are also biocompatible, being derived from natural sources and also take advantage of the enhanced permeability and retention effect due to their nanodimensions. Furthermore, CDNs derived from monocytes were shown to have an in vivo targeting effect, accumulating at the tumor site in a previous study conducted in a mouse tumor model. Here, we report a systematic approach pertaining to various loading methods of the chemotherapeutic drug doxorubicin into our CDNs and examine the differential cellular uptake of drug-loaded CDNs in cancerous (HeLa) and healthy (HEK293) cell lines. Lastly, we proved that the addition of doxorubicin-loaded CDNs to the HeLa and HEK293 co-cultures showed a clear discrimination toward cancer cells at the cellular level. Our results further reinforce the intriguing potential of CDNs as an alternative targeted strategy for anticancer therapy.

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“…One of the diseases that has been directly associated to the activation of the complement system is C activationrelated pseudoallergy (CARPA), which entails reactions of hypersensitivity. Such situations demand security evaluations and the development of technologies that consider complement activation and nanomaterials' potential to induce CARPA [74]. Complement activation has also been associated with the development and growth of tumors [75].…”

Section: Interaction Of Nanomaterials With Complement Proteinsmentioning

confidence: 99%

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

Cruz¹,

Rodríguez-Fragoso²,

JorgeReyes-Esparza³

et al. 2018

Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications

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Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials' first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood's components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary.

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Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

Cited by 85 publications

References 65 publications

Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy

Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy

Doxorubicin-loaded cell-derived nanovesicles: an alternative targeted approach for anti-tumor therapy

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

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