Novel Silibinin Loaded Chitosan-Coated PLGA/PCL Nanoparticles Based Inhalation Formulations with Improved Cytotoxicity a
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Novel Silibinin Loaded Chitosan-Coated PLGA/PCL Nanoparticles Based Inhalation Formulations with Improved Cytotoxicity and Bioavailability for Lung Cancer Mihir Raval 1 & Priya Patel 1 & Vishal Airao 1 & Vaibhav Bhatt 1 & Navin Sheth 2 Accepted: 6 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Silibinin is widely used as an anticancer agent. There are important matters of concern regarding the drug pharmacokinetics related to the conventional formulation due to their low solubility and bioavailability. The aim of the present investigation was to develop, characterize, and evaluate chitosan-coated PLGA/PCL nanoparticles containing Silibinin (SB) intended for pulmonary delivery for treating lung cancer. Nanoparticles were prepared by double emulsion solvent evaporation method followed by lyophilized to obtain inhalation powder form. The prepared nanoparticles (NPs) were evaluated for their physicochemical characteristic along with DSC, FTIR, and SEM. The anticancer activity of SB-loaded NPs was assessed in the human A549 lung cancer cell line utilizing MTT assay and anti-cancer potential assessed by clonogenic assay. The pharmacokinetics and tissue distribution studies of SB-loaded NPs were assessed in comparison with the SB solution. The prepared NPs exhibited particle sizes in the range of 187–284 nm. Zeta potential was altered from negative to positive due to the coating with chitosan. Chitosan-coated NPs showed the sustain release effect up to 48 h with an aerodynamic particle size of 1.82 μm. Moreover, a tremendous increase in cell inhibition was determined by chitosan-coated PLGA NPs. Pharmacokinetics study showed that chitosan coating onto PLGA nanoparticles promoted to release drug in the lungs and increased vivo residence time. Thus, proposed formulations with improved bioavailability can be useful for efficient pulmonary delivery. These nanoparticles coated with chitosan could open a new avenue for effective treatment of lung cancer. Keywords Silibinin . Chitosan . PLGA . PCL . MTT assay . Pharmacokinetics . Inhalation
1 Introduction On the row of cancer, lung cancer state in second place worldwide with a survival rate of only 20% [1]. As per American Cancer Society (ACS), the chances of developing lung cancer in the USA are alarming approximately 180,000 individuals are diagnosed with lung cancer every year. Chemotherapy, radiation, and surgery are the common way for the treatment Supplementary Information The online version of this article (https:// doi.org/10.1007/s12668-020-00797-z) contains supplementary material, which is available to authorized users. * Priya Patel [email protected] 1
Department of Pharmaceutical Sciences, Saurashtra University, Rajkot 360005, Gujatrat, India
2
Gujatrat Technological University, Ahmedabad 382424, Gujarat, India
of lung cancer. Chemotherapy as a traditional treatment for lung cancer has inconsistent results due to drug resistance and it is very important that these therapies be modified using modern methods [2]. Po
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