QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite

Abstract The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydr...

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Main Authors: Namrata Gautam, Debopriya Dutta, Saurabh Mittal, Perwez Alam, Nasr A. Emad, Mohamed H. Al-Sabri, Suraj Pal Verma, Sushama Talegaonkar
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-85463-8
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author Namrata Gautam
Debopriya Dutta
Saurabh Mittal
Perwez Alam
Nasr A. Emad
Mohamed H. Al-Sabri
Suraj Pal Verma
Sushama Talegaonkar
author_facet Namrata Gautam
Debopriya Dutta
Saurabh Mittal
Perwez Alam
Nasr A. Emad
Mohamed H. Al-Sabri
Suraj Pal Verma
Sushama Talegaonkar
author_sort Namrata Gautam
collection DOAJ
description Abstract The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption. The developed nanoparticles were optimized by "Design-Expert" software and underwent comprehensives in-vitro and in-vivo characterizations. The particle sizes of HAPNPs and DZHAPNPs were found to be 118.9 ± 0.15 nm and 129.3 ± 0.65 nm, respectively, consistent with their FESEM and TEM images. A notable entrapment efficiency of 87.23 ± 0.97% and drug release of 91 ± 0.85% from DZHAPNPs was observed over 90 h at pH 7.4. Moreover, the XRD and FTIR results confirmed the amorphization and compatibility of DZHAPNPs. TGA analysis indicated that the thermal stability of blank and drug-loaded nanoparticles was up to 900 °C. In an in vivo pharmacokinetic investigation, three-fold increased bioavailability of DZHAPNPs (AUC0−∞ = 7427.6 µg/mL*h) was obtained in comparison to daidzein solution (AUC0−∞ = 2299.7 µg/mL*h). The comprehensive results of the study indicate that bioceramic nanoparticles are potential carriers for DZ delivery.
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spelling doaj-art-d507c7610e264c9abd0b961b5c14cc062025-01-26T12:33:11ZengNature PortfolioScientific Reports2045-23222025-01-0115112110.1038/s41598-025-85463-8QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatiteNamrata Gautam0Debopriya Dutta1Saurabh Mittal2Perwez Alam3Nasr A. Emad4Mohamed H. Al-Sabri5Suraj Pal Verma6Sushama Talegaonkar7Department of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research UniversityDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research UniversityDepartment of Pharmaceutics, Amity Institute of Pharmacy, Amity UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutics, School of Pharmaceutical Education and ResearchDepartment of Pharmaceutical Bioscience, BMC, Uppsala UniversityDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research UniversityDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences & Research UniversityAbstract The repercussions of hormone replacement therapy (HRT) and bisphosphonates pose serious clinical challenges and warrant novel therapies for osteoporosis in menopausal women. To confront this issue, the present research aimed to design and fabricate daidzein (DZ); a phytoestrogen-loaded hydroxyapatite nanoparticles to mimic and compensate for synthetic estrogens and biomineralization. Hypothesizing this bimodal approach, hydroxyapatite nanoparticles (HAPNPs) were synthesized using the chemical-precipitation method followed by drug loading (DZHAPNPs) via sorption. The developed nanoparticles were optimized by "Design-Expert" software and underwent comprehensives in-vitro and in-vivo characterizations. The particle sizes of HAPNPs and DZHAPNPs were found to be 118.9 ± 0.15 nm and 129.3 ± 0.65 nm, respectively, consistent with their FESEM and TEM images. A notable entrapment efficiency of 87.23 ± 0.97% and drug release of 91 ± 0.85% from DZHAPNPs was observed over 90 h at pH 7.4. Moreover, the XRD and FTIR results confirmed the amorphization and compatibility of DZHAPNPs. TGA analysis indicated that the thermal stability of blank and drug-loaded nanoparticles was up to 900 °C. In an in vivo pharmacokinetic investigation, three-fold increased bioavailability of DZHAPNPs (AUC0−∞ = 7427.6 µg/mL*h) was obtained in comparison to daidzein solution (AUC0−∞ = 2299.7 µg/mL*h). The comprehensive results of the study indicate that bioceramic nanoparticles are potential carriers for DZ delivery.https://doi.org/10.1038/s41598-025-85463-8Calcium-phosphateHydroxyapatiteDaidzeinPharmacokineticsNanoparticles
spellingShingle Namrata Gautam
Debopriya Dutta
Saurabh Mittal
Perwez Alam
Nasr A. Emad
Mohamed H. Al-Sabri
Suraj Pal Verma
Sushama Talegaonkar
QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
Scientific Reports
Calcium-phosphate
Hydroxyapatite
Daidzein
Pharmacokinetics
Nanoparticles
title QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
title_full QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
title_fullStr QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
title_full_unstemmed QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
title_short QbD-Driven preparation, characterization, and pharmacokinetic investigation of daidzein-l oaded nano-cargos of hydroxyapatite
title_sort qbd driven preparation characterization and pharmacokinetic investigation of daidzein l oaded nano cargos of hydroxyapatite
topic Calcium-phosphate
Hydroxyapatite
Daidzein
Pharmacokinetics
Nanoparticles
url https://doi.org/10.1038/s41598-025-85463-8
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