TY - JOUR
T1 - Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41
AU - Cordeiro, Teresa
AU - Matos, Inês
AU - Danède, Florence
AU - Sotomayor, João C.
AU - Fonseca, Isabel M.
AU - Corvo, Marta C.
AU - Dionísio, Madalena
AU - Viciosa, María Teresa
AU - Affouard, Frédéric
AU - Correia, Natália T.
N1 - Funding Information:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F50006%2F2019/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00100%2F2020/PT#
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00100%2F2020/PT#
info:eu-repo/grantAgreement/FCT/9444 - RNIIIE/PINFRA%2F22161%2F2016/PT#
info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F114653%2F2016/PT#
info:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F01242%2F2014%2FCP1224%2FCT0008/PT#
co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER—007265).
This research was funded by the Interreg 2 Seas program 2014–2020, and co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01-059_IMODE and 2S07-033_ Site Drug.
This research was funded by the Program PHC PESSOA 2018 project nbr 4340/40868R.
This research was funded by National Funds through FCT—Portuguese Foundation for Science and Technology, reference, LA/P/0056/2020, UIDB/50025/2020-2023, and PTNMR (ROTEIRO/0031/2013), co-financed by ERDF through COMPETE 2020, Portugal, POCI and PORL and FCT through PIDDAC (POCI-01-0145-FEDER-007688).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/4/22
Y1 - 2023/4/22
N2 - A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.
AB - A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.
KW - amorphous state
KW - drug delivery development
KW - drug release
KW - drug-carrier multiple interactions
KW - molecular mobility
KW - simvastatin
UR - http://www.scopus.com/inward/record.url?scp=85160394158&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics15051320
DO - 10.3390/pharmaceutics15051320
M3 - Article
C2 - 37242562
AN - SCOPUS:85160394158
SN - 1999-4923
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 5
M1 - 1320
ER -