Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method

Oluwatomide Adeoye, Jaime Conceição, Patrícia A. Serra, Andreia Bento da Silva, Noélia Duarte, Rita C. Guedes, Marta C. Corvo, Ana Aguiar-Ricardo, László Jicsinszky, Teresa Casimiro, Helena Cabral-Marques

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number115287
JournalCarbohydrate Polymers
Volume227
DOIs
Publication statusPublished - 1 Jan 2020

Fingerprint

Lopinavir
Cyclodextrins
Complexation
Pharmaceutical Preparations
Spray drying
Ritonavir
Molecular interactions
Amorphization
Evaporation
Substitution reactions
Derivatives

Keywords

  • (2-Hydroxy)propyl-γ-cyclodextrin
  • Aluviran
  • HIV/AIDS
  • Molecular docking and dynamics
  • Supercritical fluid assisted spray drying

Cite this

Adeoye, Oluwatomide ; Conceição, Jaime ; Serra, Patrícia A. ; Bento da Silva, Andreia ; Duarte, Noélia ; Guedes, Rita C. ; Corvo, Marta C. ; Aguiar-Ricardo, Ana ; Jicsinszky, László ; Casimiro, Teresa ; Cabral-Marques, Helena. / Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method. In: Carbohydrate Polymers. 2020 ; Vol. 227.
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abstract = "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.",
keywords = "(2-Hydroxy)propyl-γ-cyclodextrin, Aluviran, HIV/AIDS, Molecular docking and dynamics, Supercritical fluid assisted spray drying",
author = "Oluwatomide Adeoye and Jaime Concei{\cc}{\~a}o and Serra, {Patr{\'i}cia A.} and {Bento da Silva}, Andreia and No{\'e}lia Duarte and Guedes, {Rita C.} and Corvo, {Marta C.} and Ana Aguiar-Ricardo and L{\'a}szl{\'o} Jicsinszky and Teresa Casimiro and Helena Cabral-Marques",
note = "This work was supported in part by iMed.ULisboa, financed by national funds from FCT/MCTES UID/DTP/04138/2019; projects PTDC/EQU-EQU/32473/2017 and IF/00915/2014; Associate Laboratory for Green Chemistry LAQV-REQUIMTE which is financed by national funds from FCT/MCTES (UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER -007265); Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa - RNEM; LISBOA-01-0145-FEDER-402-022125); UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019) and by i3N and RNRMN financed by national funds from FCT/MCTES (UID/CTM/50025/2013, ROTEIRO/0031/2013 - PINFRA/22161/2016), co-financed by the ERDF under European funds through the COMPETE 2020 Program, Portugal (POCI-01-0145-FEDER-007688). OA acknowledges partial PhD scholarship funding from the Tertiary Education Fund (TETFUND) of Nigeria; while JC acknowledges Portuguese FCT/i3DU for the grant - PD/BD/127813/2016.",
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Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method. / Adeoye, Oluwatomide; Conceição, Jaime; Serra, Patrícia A.; Bento da Silva, Andreia; Duarte, Noélia; Guedes, Rita C.; Corvo, Marta C.; Aguiar-Ricardo, Ana; Jicsinszky, László; Casimiro, Teresa; Cabral-Marques, Helena.

In: Carbohydrate Polymers, Vol. 227, 115287, 01.01.2020.

Research output: Contribution to journalArticle

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 - This work was supported in part by iMed.ULisboa, financed by national funds from FCT/MCTES UID/DTP/04138/2019; projects PTDC/EQU-EQU/32473/2017 and IF/00915/2014; Associate Laboratory for Green Chemistry LAQV-REQUIMTE which is financed by national funds from FCT/MCTES (UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER -007265); Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa - RNEM; LISBOA-01-0145-FEDER-402-022125); UCIBIO which is financed by national funds from FCT/MCTES (UID/Multi/04378/2019) and by i3N and RNRMN financed by national funds from FCT/MCTES (UID/CTM/50025/2013, ROTEIRO/0031/2013 - PINFRA/22161/2016), co-financed by the ERDF under European funds through the COMPETE 2020 Program, Portugal (POCI-01-0145-FEDER-007688). OA acknowledges partial PhD scholarship funding from the Tertiary Education Fund (TETFUND) of Nigeria; while JC acknowledges Portuguese FCT/i3DU for the grant - PD/BD/127813/2016.

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

VL - 227

JO - Carbohydrate Polymers

JF - Carbohydrate Polymers

SN - 0144-8617

M1 - 115287

ER -