Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

Vancha Harish; Devesh Tewari; Sharfuddin Mohd; Pilli Govindaiah; Malakapogu Ravindra Babu; Rajesh Kumar; Monica Gulati; Kuppusamy Gowthamarajan; Subba Rao V. Madhunapantula; Dinesh Kumar Chellappan; Gaurav Gupta; Kamal Dua; Siva Dallavalasa; Sachin Kumar Singh

doi:10.3390/pharmaceutics14112403

Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

Vancha Harish
, Devesh Tewari
, Sharfuddin Mohd
, Pilli Govindaiah
, Malakapogu Ravindra Babu
, Rajesh Kumar
, Monica Gulati
, Kuppusamy Gowthamarajan
, Subba Rao V. Madhunapantula
, Dinesh Kumar Chellappan
, Gaurav Gupta
, Kamal Dua
, Siva Dallavalasa
, Sachin Kumar Singh

Lovely Professional University
Delhi Pharmaceutical Sciences and Research University
Wayne State University
University of Technology Sydney
JSS Academy of Higher Education & Research
International Medical University
Suresh Gyan Vihar University
Saveetha Institute of Medical and Technical Sciences (Deemed to be University)
Uttaranchal University

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in C_max (1.07-folds), AUC_0-t (4.70-folds), t_1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.

Original language	English
Article number	2403
Journal	Pharmaceutics
Volume	14
Issue number	11
DOIs	https://doi.org/10.3390/pharmaceutics14112403
State	Published - Nov 2022
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Box–Behnken Design
Xanthohumol
drug release
oral bioavailability
solid lipid nanoparticles

Access to Document

10.3390/pharmaceutics14112403

Cite this

Harish, V., Tewari, D., Mohd, S., Govindaiah, P., Babu, M. R., Kumar, R., Gulati, M., Gowthamarajan, K., Madhunapantula, S. R. V., Chellappan, D. K., Gupta, G., Dua, K., Dallavalasa, S., & Singh, S. K. (2022). Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells. Pharmaceutics, 14(11), Article 2403. https://doi.org/10.3390/pharmaceutics14112403

@article{da8d3436edc54d8dbb1e98bafc9231c1,

title = "Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells",

abstract = "Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), \%EE (80.20\%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40\% in 12 h for naive XH, whereas only 28.42\% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in Cmax (1.07-folds), AUC0-t (4.70-folds), t1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791\% and 20.80\%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.",

keywords = "Box–Behnken Design, Xanthohumol, drug release, oral bioavailability, solid lipid nanoparticles",

author = "Vancha Harish and Devesh Tewari and Sharfuddin Mohd and Pilli Govindaiah and Babu, \{Malakapogu Ravindra\} and Rajesh Kumar and Monica Gulati and Kuppusamy Gowthamarajan and Madhunapantula, \{Subba Rao V.\} and Chellappan, \{Dinesh Kumar\} and Gaurav Gupta and Kamal Dua and Siva Dallavalasa and Singh, \{Sachin Kumar\}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

doi = "10.3390/pharmaceutics14112403",

language = "English",

volume = "14",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "11",

}

Harish, V, Tewari, D, Mohd, S, Govindaiah, P, Babu, MR, Kumar, R, Gulati, M, Gowthamarajan, K, Madhunapantula, SRV, Chellappan, DK, Gupta, G , Dua, K, Dallavalasa, S & Singh, SK 2022, 'Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells', Pharmaceutics, vol. 14, no. 11, 2403. https://doi.org/10.3390/pharmaceutics14112403

TY - JOUR

T1 - Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

AU - Harish, Vancha

AU - Tewari, Devesh

AU - Mohd, Sharfuddin

AU - Govindaiah, Pilli

AU - Babu, Malakapogu Ravindra

AU - Kumar, Rajesh

AU - Gulati, Monica

AU - Gowthamarajan, Kuppusamy

AU - Madhunapantula, Subba Rao V.

AU - Chellappan, Dinesh Kumar

AU - Gupta, Gaurav

AU - Dua, Kamal

AU - Dallavalasa, Siva

AU - Singh, Sachin Kumar

PY - 2022/11

Y1 - 2022/11

N2 - Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in Cmax (1.07-folds), AUC0-t (4.70-folds), t1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.

AB - Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in Cmax (1.07-folds), AUC0-t (4.70-folds), t1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells.

KW - Box–Behnken Design

KW - Xanthohumol

KW - drug release

KW - oral bioavailability

KW - solid lipid nanoparticles

UR - https://www.scopus.com/pages/publications/85149123692

U2 - 10.3390/pharmaceutics14112403

DO - 10.3390/pharmaceutics14112403

M3 - Article

AN - SCOPUS:85149123692

SN - 1999-4923

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

IS - 11

M1 - 2403

ER -

Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

Abstract

UN SDGs

Keywords

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