Polymeric nanocapsular baicalin: Chemometric optimization, physicochemical characterization and mechanistic anticancer approaches on breast cancer cell lines

Riham I El-Gogary,Maha Nasr,Sara A Abdel Gaber

doi:10.1038/s41598-019-47586-7

Riham I El-Gogary, Maha Nasr + Show 1 more

Open Access

https://doi.org/10.1038/s41598-019-47586-7

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Journal: Scientific Reports	Publication Date: Jul 30, 2019
Citations: 56	License type: open-access

Affiliation: Ain Shams University, Kafrelsheikh University

Abstract

Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability. Polymeric nanocapsules were proposed in this work as a promising system for enhancing baicalin delivery, and potentiating its anticancer properties. The characterization of nanocapsules was augmented with chemometric analysis, and the selected formulations were tested on two breast cancer cell lines (MCF-7 and MDA-MB-231), with mechanistic anticancer elucidation using MTT assay, confocal microscopy uptake, flow cytometry, mechanism of cell death, reactive oxygen species production, caspase 3/7 activity and death biomarker expression using quantitative real time PCR. Results showed that baicalin nanocapsules displayed favorable pharmaceutical properties; with the formulation variables affecting their properties elucidated using chemometric factorial analysis. Nanocapsules enhanced the anticancer activity of baicalin up to 216 times for MCF-7 cells and 31 times for MDA-MB-231 after 24 hr incubation. Cellular internalization of the fluorescently labeled nanocapsules was confirmed after 4 hr incubation for both cell lines. Apoptosis was the dominant cell death mechanism, with significant up-regulation of P53 in baicalin nanocapsules treated cells. Data here presented drive to further preclinical studies to investigate the delivery of baicalin polymeric nanocapsules and their anti-cancer activity.

Highlights

Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability
Baicalin nanocapsules were successfully prepared as a novel delivery system for the anticancer baicalin
The oily core of the nanocapsules was constituted by a corn oil pegylated ester (Labrafil M2125 CS), providing the highest solubility for baicalin, based on a preliminary conducted solubility study

Summary

Introduction

Baicalin is a multi-purpose flavonoid known for its anticancer properties, but its application is hindered by its low water solubility and bioavailability. Polymeric nanocapsules were proposed in this work as a promising system for enhancing baicalin delivery, and potentiating its anticancer properties. In order to enhance its bioavailability and effectiveness in cancer treatment, baicalin was formulated in different nanoparticulate systems, such as liposomes[3,13] and solid lipid nanoparticles[2]. Gold nanoparticles were conjugated with baicalin and the conjugate induced a more prominent apoptosis in breast cancer cell line MCF-716. Are known for their long-term toxic effects[17] In this regard, the use of biocompatible and biodegradable polymers is favored. A promising biodegradable nanoparticulate system which was proven effective in cancer treatment is polymeric nanocapsules[18,19,20]. Polylactide-glycolide (PLGA) is a commonly used polymer for the preparation of nanocapsules, owing to its biodegradability, as well as its ability to be tailored for active targeting by covalent attachment of targeting ligands to its acid terminated functional groups

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