Covalently coupling doxorubicin to polymeric nanoparticles as potential inhaler therapy: in vitro studies

Abstract

Lung cancer is the most commonly diagnosed type of cancer worldwide, non-small cell lung cancer accounts for most lung cancers. Doxorubicin is a widely used chemotherapy agent in lung cancer. However, the drug has several undesirable side effects. Here, doxorubicin coupled PEGylated mucoadhesive nanoparticles were designed as a doxorubicin delivery system for pH-triggered release in lung cancer therapy through inhaler administration. Firstly, alginate/chitosan nanoparticles were developed at optimum conditions. Then, PEG diacid bound to structures for doxorubicin binding and providing steric hindrance for phagocytosis. Doxorubicin was linked via an acid–labile amide bond to PEGylated nanoparticles and 444.3 ± 9.2 µg doxorubicin was loaded per mg nanoparticle. Doxorubicin coupled PEG diacid linked alginate/chitosan nanoparticles were checked with FTIR. Hydrodynamic diameter and zeta potential of nanoparticles were measured as 205.7 ± 15.0 nm and −25.17 ± 2.67 mV. The morphology of nanoparticles was evaluated as nearly spherical. Drug release studies were performed both in physiological and acidic media. The drug release from nanoparticles reached 23.6% (pH 5.5) and 18% (pH 7.4) within 48 h. The cytotoxicity experiments were done using A549-luc-C8 cells, also statistical analyzes were carried out. The MTT results indicated the designed drug delivery system possessed anti-tumor efficacy for non-small cell lung cancer therapy.

Graphical Abstract

Keywords:

• Doxorubicin
• inhaler therapy
• alginate chitosan nanoparticle
• drug delivery
• lung cancer

Acknowledgment

I would like to acknowledge to Ege University Drug Development and Pharmacokinetics Research – Application Center (ARGEFAR). I would also thank to Buket Özel and Dursun Demiroz for helping with cell culture and statistical analyzes.

Disclosure statement

The author reports no conflict of interest. Patent application in the national area has been filed for this invention, which has been supported by Ege University (2020/19415).

Additional information

Funding

This work was supported by the Research Foundation of Ege University [Grant number, 17 FEN 014].