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Core‐Shell Functionalized Zirconium‐Pemetrexed Coordination Nanoparticles as Carriers with a High Drug Content
Author(s) -
Steinborn Benjamin,
Hirschle Patrick,
Höhn Miriam,
Bauer Tobias,
Barz Matthias,
Wuttke Stefan,
Wagner Ernst,
Lächelt Ulrich
Publication year - 2019
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201900120
Subject(s) - zirconium , nanoparticle , chemistry , molecule , drug delivery , drug , pemetrexed , nanomaterials , combinatorial chemistry , polymer , nanotechnology , materials science , inorganic chemistry , organic chemistry , pharmacology , medicine , surgery , chemotherapy , cisplatin
Selected drug molecules with Lewis base functions can be assembled into coordinative nanoparticles (NPs) by linking them with suitable metal ions. Such nanomaterials exhibit a high material economy due to high drug contents and minor amounts of inactive additives. The antifolate pemetrexed (PMX) which is used for the treatment of lung cancers contains two carboxy functions that are able to undergo coordinative binding of metal ions. This study presents the development of a multilayer PMX NP system where each layer serves a distinct purpose. The metal‐drug NP core is assembled in a bottom‐up approach by coordinative interactions between zirconium (IV) ions and PMX molecules. Since the NP core is generated from drug molecules as essential units, it features a very high drug content of almost 80%. The NP core is stabilized against serum with a shell of a polymerized oligoamine‐modified trimethoxysilane derivative (TMSP). As external layer, a polyglutamate‐ block ‐polysarcosine‐N 3 (pGlu‐ b ‐pSar) coating mediates efficient colloidal stabilization and enables introduction of targeting functionalities by click chemistry. Attaching folate or transferrin ligands to the polymer layer enhances NP uptake into target receptor positive KB and L1210 cells. This study illustrates the development and characterization of metal‐drug coordination NPs with high drug content and variable external functionalizations.