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 mu g 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.