Flow cytometric analysis of supravesicular structures in doxorubicin-containing pegylated liposomes

Complement activation in vitro and reactogenicity of low-molecular weight dextran-coated SPIONs in the pig CARPA model: Correlation with physicochemical features and clinical information

“…Our data suggest stronger C activation and stronger in vivo reactivity of Sinerem compared to Resovist, which is consistent with the information that HSRs contributed to the withdrawal from the market of Sinerem [16], but not that of Resovist [17,18]. We can also correlate the C activation data with at least one particle feature known to contribute to C activation and CARPA: inhomogeneity [44]. While the DLS average size info (Table 1) showed no difference, the NTA analysis revealed more expressed inhomogeneity in Sinerem than in Resovist, which could be due to increased amounts of aggregates in the latter preparation.…”

“…Of note, NTA has a detection limit around 30 nm and only particles above this minimum size (i.e., in this case, SPION aggregates) can be observed with this technique [43]. Taken together, the NTA measurements suggest that a possible underlying factor behind the increased C activating and CARPAgenic activity of Sinerem is the increased size and inhomogeneity of NPs in it, with possible presence of aggregates, which are known contributors to C activation and HSRs [44]. Regarding the role of aggregates, however, it needs to be pointed out that our test samples were not freshly opened original vials, and they were not filtered before application although the product insert of Sinerem, but not that of Resovist, recommends filtering of the infusate before human application to get rid of possible aggregates.…”

Complement activation-related pseudoallergy: A stress reaction in blood triggered by nanomedicines and biologicals

“…Moreover, a previous study provided evidence for the presence of an exceedingly small fraction (60 billionth part) of >500 nm particles in Doxil and other PEGylated liposome suspension (Milosevits et al, 2012). Thus, if Ig binding to molecular aggregates can mimic Ig aggregates, aggregates may provide possible triggers for C activation by liposomes.…”

Mannose modified co-loaded zoledronic liposomes deplete M2-tumor-associated macrophages to enhance anti-tumor effect of doxorubicin on TNBC

“…Nanotechnology, particularly nanoparticle and liposome-based drug delivery systems, can improve pharmacokinetics, targeted delivery, and reduced toxicity [6]. At present, Doxil/Caelyx liposomes (Doxil®/Caelyx®) have been translated into clinical applications [7]. Although the toxicity is reduced, its anti-tumor effect has not increased signi cantly.…”