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European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Unique therapeutic properties and preparation methodology of multivalent rituximab-lipid nanoparticles.


PMID 28450189

Abstract

Therapeutic monoclonal antibodies hold great promise in the treatment of cancer and other diseases, but their unclear mechanism of action makes it difficult to identify features that will increase their efficacy. One such feature may be antibody valence, since enhanced therapeutic efficacies have been observed using multivalent, as opposed to bivalent, antibodies. For example, multivalent antibody-lipid nanoparticles (Ab-LNPs) containing rituximab (Rtx) or trastuzumab show significantly increased therapeutic activity compared to equivalent doses of the bivalent antibodies. To more fully understand this phenomenon, we created a methodology reliant on biotin-neutravidin interactions for preparing specific valences of Ab-LNPs that shows improvements in reproducibility, preparation time and overall yield of coupled Ab (up to 80%). We subsequently prepared a series of valences of Rtx-LNPs to examine binding characteristics to CD20