"Tandem" Nanomedicine Approach against Osteoclastogenesis: Polysulfide Micelles Synergically Scavenge ROS and Release Rapamycin.
Biomacromolecules
; 21(2): 305-318, 2020 02 10.
Article
en En
| MEDLINE
| ID: mdl-31793790
ABSTRACT
We show the first example of a synergic approach of oxidant (ROS) scavenging carrier and ROS-responsive drug release in the context of a potential therapy against osteoporosis, aiming to inhibit the differentiation of inflammatory cells into osteoclasts. In our "tandem" approach, a branched amphiphilic, PEGylated polysulfide (PPSES-PEG) was preferred over a linear analogue, because of improved homogeneity in the aggregates (spherical micelles vs mixture of wormlike and spherical), increased stability, and higher drug loading (up to â¼22 wt % of antiosteoclastic rapamycin). These effects are ascribed to the branching inhibiting crystallization in the polysulfide blocks. The ROS-scavenging micelles alone were already able to reduce osteoclastogenesis in a RAW 264.7 model, but the "drug" combination (the polymer itself + rapamycin released only under oxidation) completely abrogated the process. An important take-home message is that the synergic performance depended very strongly on the oxidantoxidizable group molar ratio, a parameter to carefully tune in the perspective of targeting specific diseases.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Osteogénesis
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Portadores de Fármacos
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Sirolimus
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Nanomedicina
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Micelas
Idioma:
En
Revista:
Biomacromolecules
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article