A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylatedtrifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almostmonodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potentialof −27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPSwere elucidated by comparing copolymers and glucocorticoids with different structure. The micellarstructure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with bloodserum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxi-city in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportationand hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometrywith multiple reaction monitoring which showed increased level of both MPS and methylprednisolonein neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as anadvanced in situ prepared nanoformulation and encourage its further investigation for a potential localglucocorticoid therapy.
Bibliographical note© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
- Methylprednisolone succinate
- Ethylene oxide and propylene oxide copolymers
- Mixed micelles
- Cellular availability
- Mass spectrometry
- Local glucocorticoid therapy