TY - JOUR
T1 - Cyclodextrin based bone regenerative inclusion complex for resveratrol in postmenopausal osteoporosis
AU - Shah, Aarti Abhishek
AU - Shah, Abhishek
AU - Lewis, Shaila
AU - Ghate, Vivek
AU - Saklani, Ravi
AU - Narayana Kalkura, S.
AU - Baby, C.
AU - Singh, Pankaj Kumar
AU - Nayak, Yogendra
AU - Chourasia, Manish K.
N1 - Funding Information:
The authors are grateful to the Cambridge Crystallographic Data Centre (CCDC), UK, for providing access to the Mercury® and GOLD® software (2016) for carrying out the molecular modeling and simulation studies. The authors are also thankful to PerkinElmer, UK, for providing trial access to the fully functional version of ChemOffice 2015 while carrying out the molecular simulation studies. The authors acknowledge the Sophisticated Analytical Instrument Facility (SAIF), from IIT, Madras to carry out 1 H NMR, 2-D ROSEY, and DSC analysis studies. We want to acknowledge the support received from Crystal Growth Centre, Anna University, Chennai for assisting formulation and support in FTIR and XRD studies. We also wish to acknowledge the Central Animal Research Facility (CARF), Manipal Academy of Higher Education, Manipal for providing the animal facility to carry out this research work. We thank Dr. Naibedya Chattopadhyay and Ms. Konica Porwal from Central Drug Research Institute, Lucknow to receive support for µ-CT scanning, and biomechanical strength of the rat femur bones. Dr. Narayana Subbaraya Kalkura is thankful to the University Grants Commission, India for the award of the UGC-BSR Faculty Fellowship. The CSIR-CDRI Communication Number of this manuscript is 10271.
Funding Information:
This study was financially supported by the Department of Science and Technology, Government of India (reference no. SR/WOS-A/LS-444/2016) under the women scientist scheme-A (WOS-A).
Funding Information:
The authors are grateful to the Cambridge Crystallographic Data Centre (CCDC), UK, for providing access to the Mercury? and GOLD? software (2016) for carrying out the molecular modeling and simulation studies. The authors are also thankful to PerkinElmer, UK, for providing trial access to the fully functional version of ChemOffice 2015 while carrying out the molecular simulation studies. The authors acknowledge the Sophisticated Analytical Instrument Facility (SAIF), from IIT, Madras to carry out 1H NMR, 2-D ROSEY, and DSC analysis studies. We want to acknowledge the support received from Crystal Growth Centre, Anna University, Chennai for assisting formulation and support in FTIR and XRD studies. We also wish to acknowledge the Central Animal Research Facility (CARF), Manipal Academy of Higher Education, Manipal for providing the animal facility to carry out this research work. We thank Dr. Naibedya Chattopadhyay and Ms. Konica Porwal from Central Drug Research Institute, Lucknow to receive support for ?-CT scanning, and biomechanical strength of the rat femur bones. Dr. Narayana Subbaraya Kalkura is thankful to the University Grants Commission, India for the award of the UGC-BSR Faculty Fellowship. The CSIR-CDRI Communication Number of this manuscript is 10271. This study was financially supported by the Department of Science and Technology, Government of India (reference no. SR/WOS-A/LS-444/2016) under the women scientist scheme-A (WOS-A).
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/10
Y1 - 2021/10
N2 - Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether β-cyclodextrin (SBE-β-CD) to enhance the aqueous solubility of RSV. The in-silico docking studies and Physico-chemical characterization assays were performed to understand the interaction of RSV inside the SBE-β-CD cavity. The in vivo safety assessment of RSV-SBE-β-CD inclusion complex (R-CDIC) was performed in healthy Wistar rats. The efficacy of the inclusion complex against postmenopausal osteoporosis was further investigated in ovariectomized (OVX) rat model. The alteration in the bone micro-architectural structure was evaluated by microcomputed tomographic scanning, serum biochemical estimations, biomechanical strength and histopathological investigation. Administration of RSV-SBE-β-CD inclusion complex was found to be safe and significantly improved micro-architectural deterioration induced by estrogen withdrawal. Results of bone morphometry and biomechanics study further emboldened the efficacy claim of the RSV-SBE-β-CD complex. Thus, the present study demonstrated the efficacy of the RSV-SBE-β-CD inclusion complex for treating osteolytic degradation in osteoporosis.
AB - Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether β-cyclodextrin (SBE-β-CD) to enhance the aqueous solubility of RSV. The in-silico docking studies and Physico-chemical characterization assays were performed to understand the interaction of RSV inside the SBE-β-CD cavity. The in vivo safety assessment of RSV-SBE-β-CD inclusion complex (R-CDIC) was performed in healthy Wistar rats. The efficacy of the inclusion complex against postmenopausal osteoporosis was further investigated in ovariectomized (OVX) rat model. The alteration in the bone micro-architectural structure was evaluated by microcomputed tomographic scanning, serum biochemical estimations, biomechanical strength and histopathological investigation. Administration of RSV-SBE-β-CD inclusion complex was found to be safe and significantly improved micro-architectural deterioration induced by estrogen withdrawal. Results of bone morphometry and biomechanics study further emboldened the efficacy claim of the RSV-SBE-β-CD complex. Thus, the present study demonstrated the efficacy of the RSV-SBE-β-CD inclusion complex for treating osteolytic degradation in osteoporosis.
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U2 - 10.1016/j.ejpb.2021.07.008
DO - 10.1016/j.ejpb.2021.07.008
M3 - Article
AN - SCOPUS:85112367191
SN - 0939-6411
VL - 167
SP - 127
EP - 139
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -