TY - JOUR
T1 - Modulation of metal-azolate frameworks for the tunable release of encapsulated glycosaminoglycans
AU - Velásquez-Hernández, Miriam De J.
AU - Astria, Efwita
AU - Winkler, Sarah
AU - Liang, Weibin
AU - Wiltsche, Helmar
AU - Poddar, Arpita
AU - Shukla, Ravi
AU - Prestwich, Glenn
AU - Paderi, John
AU - Salcedo-Abraira, Pablo
AU - Amenitsch, Heinz
AU - Horcajada, Patricia
AU - Doonan, Christian J.
AU - Falcaro, Paolo
PY - 2020/10/21
Y1 - 2020/10/21
N2 - Glycosaminoglycans (GAGs) are biomacromolecules necessary for the regulation of different biological functions. In medicine, GAGs are important commercial therapeutics widely used for the treatment of thrombosis, inflammation, osteoarthritis and wound healing. However, protocols for the encapsulation of GAGs in MOFs carriers are not yet available. Here, we successfully encapsulated GAG-based clinical drugs (heparin, hyaluronic acid, chondroitin sulfate, dermatan sulfate) and two new biotherapeutics in preclinical stage (GM-1111 and HepSYL proteoglycan) in three different pH-responsive metal-azolate frameworks (ZIF-8, ZIF-90, and MAF-7). The resultant GAG@MOF biocomposites present significant differences in terms of crystallinity, particle size, and spatial distribution of the cargo, which influences the drug-release kinetics upon applying an acidic stimulus. For a selected system, heparin@MOF, the released therapeutic retained its antithrombotic activity while the MOF shell effectively protects the drug from heparin lyase. By using different MOF shells, the present approach enables the preparation of GAG-based biocomposites with tunable properties such as encapsulation efficiency, protection and release.
AB - Glycosaminoglycans (GAGs) are biomacromolecules necessary for the regulation of different biological functions. In medicine, GAGs are important commercial therapeutics widely used for the treatment of thrombosis, inflammation, osteoarthritis and wound healing. However, protocols for the encapsulation of GAGs in MOFs carriers are not yet available. Here, we successfully encapsulated GAG-based clinical drugs (heparin, hyaluronic acid, chondroitin sulfate, dermatan sulfate) and two new biotherapeutics in preclinical stage (GM-1111 and HepSYL proteoglycan) in three different pH-responsive metal-azolate frameworks (ZIF-8, ZIF-90, and MAF-7). The resultant GAG@MOF biocomposites present significant differences in terms of crystallinity, particle size, and spatial distribution of the cargo, which influences the drug-release kinetics upon applying an acidic stimulus. For a selected system, heparin@MOF, the released therapeutic retained its antithrombotic activity while the MOF shell effectively protects the drug from heparin lyase. By using different MOF shells, the present approach enables the preparation of GAG-based biocomposites with tunable properties such as encapsulation efficiency, protection and release.
UR - http://www.scopus.com/inward/record.url?scp=85093508221&partnerID=8YFLogxK
U2 - 10.1039/d0sc01204a
DO - 10.1039/d0sc01204a
M3 - Article
AN - SCOPUS:85093508221
SN - 2041-6520
VL - 11
SP - 10835
EP - 10843
JO - Chemical Science
JF - Chemical Science
IS - 39
ER -