TY - JOUR
T1 - Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method
AU - Adeoye, Oluwatomide
AU - Conceição, Jaime
AU - Serra, Patrícia A.
AU - Bento da Silva, Andreia
AU - Duarte, Noélia
AU - Guedes, Rita C.
AU - Corvo, Marta C.
AU - Aguiar-Ricardo, Ana
AU - Jicsinszky, László
AU - Casimiro, Teresa
AU - Cabral-Marques, Helena
N1 - UID/DTP/04138/2019.
PTDC/EQU-EQU/32473/2017. IF/00915/2014.
UID/QUI/50006/2019.
POCI-01-0145-FEDER -007265. RNEM; LISBOA-01-0145-FEDER-402-022125).
UID/Multi/04378/2019.
UID/CTM/50025/2013. ROTEIRO/0031/2013 - PINFRA/22161/2016).
POCI-01-0145-FEDER-007688.
Grant - PD/BD/127813/2016.
Sem PDF conforme despacho.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LPV delivery system. The predicted CyD, a (2-hydroxy)propyl-gamma derivative with high degree of substitution (HP17-γ-CyD) was synthesized and comparatively evaluated with γ-CyD and the commercially available HP-γ-CyD. All complexes were prepared by supercritical assisted spray drying (SASD) and co-evaporation (CoEva) at molar ratios (1:1 and 1:2); and afterwards fully characterized. Results indicate a higher LPV amorphization and solubilization ability of HP17-γ-CyD. The SASD processing technology also enhanced LPV solubilization and release from complexes. The application of in silico methodologies is a feasible approach for the rational and/or deductive development of CyD drug delivery systems.
AB - Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LPV delivery system. The predicted CyD, a (2-hydroxy)propyl-gamma derivative with high degree of substitution (HP17-γ-CyD) was synthesized and comparatively evaluated with γ-CyD and the commercially available HP-γ-CyD. All complexes were prepared by supercritical assisted spray drying (SASD) and co-evaporation (CoEva) at molar ratios (1:1 and 1:2); and afterwards fully characterized. Results indicate a higher LPV amorphization and solubilization ability of HP17-γ-CyD. The SASD processing technology also enhanced LPV solubilization and release from complexes. The application of in silico methodologies is a feasible approach for the rational and/or deductive development of CyD drug delivery systems.
KW - (2-Hydroxy)propyl-γ-cyclodextrin
KW - Aluviran
KW - HIV/AIDS
KW - Molecular docking and dynamics
KW - Supercritical fluid assisted spray drying
UR - http://www.scopus.com/inward/record.url?scp=85072659617&partnerID=8YFLogxK
U2 - 10.1016/j.carbpol.2019.115287
DO - 10.1016/j.carbpol.2019.115287
M3 - Article
C2 - 31590843
AN - SCOPUS:85072659617
SN - 0144-8617
VL - 227
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
M1 - 115287
ER -
