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

Harish V, Tewari D, Mohd S, Govindaiah P, Babu MR, Kumar R, et al.

Pharmaceutics, 2022 Nov 07;14(11).
PMID: 36365221 DOI: 10.3390/pharmaceutics14112403

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.
Exploring nanoparticular platform in delivery of repurposed drug for Alzheimer's disease: current approaches and future perspectives

Chakraborty S, Vishwas S, Harish V, Gupta G, Paudel KR, Dhanasekaran M, et al.

Expert Opin Drug Deliv, 2024 Dec;21(12):1771-1792.
PMID: 39397403 DOI: 10.1080/17425247.2024.2414768

INTRODUCTION: Alzheimer's disease (AD) stands as significant challenge in realm of neurodegenerative disorder. It is characterized by gradual decline in cognitive function and memory loss. It has already expanded its prevalence to 55 million people worldwide and is expected to rise significantly. Unfortunately, there exists a limited therapeutic option that would mitigate its progression. Repurposing existing drugs and employing nanoparticle as delivery agent presents a potential solution to address the intricate pathology of AD.
AREAS COVERED: In this review, we delve into utilization of nanoparticular platforms to enhance the delivery of repurposed drugs for treatment of AD. Firstly, the review begins with the elucidation of intricate pathology underpinning AD, subsequently followed by rationale behind drug repurposing in AD. Covered are explorations of nanoparticle-based repurposing of drugs in AD, highlighting their clinical implication. Further, the associated challenges and probable future perspective are delineated.
EXPERT OPINION: The article has highlighted that extensive research has been carried out on the delivery of repurposed nanomedicines against AD. However, there is a need for advanced and long-term research including clinical trials required to shed light upon their safety and toxicity profile. Furthermore, their scalability in pharmaceutical set-up should also be validated.

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