. 2017 May 1;38(6):782–797. doi: 10.1038/aps.2017.34

Table 2. Preclinical and clinical studies showing the safety and efficacy of nanoparticles in the pulmonary delivery of chemotherapeutic agents.

Drug	Carrier	Outcome
Paclitaxel	Polyethylene glycol₅₀₀₀-distearoylphosphatidylethanolamine	The lung targeting efficiency via the pulmonary route (PEG₅₀₀₀-DSPE) micelles was 132-fold higher than the intravenous route. Micelles substantially reduced the distribution of paclitaxel in non-targeted tissues compared with free paclitaxel following intratracheal administration. Micelles showed no sign of inflammation in lung tissues, highlighting the safety and suitability of the delivery vehicle for inhaled delivery⁷⁴.
Doxorubicin	Human serum albumin (HSA) nanoparticles adsorbed with Apoptotic TRAIL protein (TRAIL/Dox HSA-NP)	Inhaled TRAIL/Dox HSA-NP nanoparticles were distributed effectively throughout the lungs and provided sustained drug release. Inhaled TRAIL/Dox HSA-NP also expressed greater anti-tumor activity compared with TRAIL or Dox HSA-NP alone, with minimal side effects¹²⁴.
Losartan and telmisartan	Polystyrene nanoparticles	Losartan and Telmisartan showed significant in vivo anticancer activity against orthotopic and metastatic lung cancers. Animals receiving inhaled losartan and Telmisartan survived longer than untreated animals. The drugs were well tolerated by normal lung tissues¹¹⁹.
Doxorubicin	56-kDa PEGylated-polylysine dendrimer	The dendrimer expressed improved anti-tumor activity following intratracheal administration compared with the drug solution administered intravenously. The drug-dendrimer complex was better tolerated by the lungs than free drug after intratracheal administration⁹⁰.
Epirubicin	Solid lipid nanoparticles	Epirubicin concentration in the lungs was higher than in plasma following inhaled nanoparticle therapy. The drug concentration in the lungs was higher with inhaled epirubicin nanoparticles compared with inhaled epirubicin solution¹²⁵.
9-Bromo-noscapine (9-Br-Nos) Doxorubicin and cisplatin,two types of siRNA targeted to MRP1 and BCL2 mRNAs	Nanostructured lipid particles (NLPs) Luteinizing hormone-releasing hormone receptor-targeted mesoporous silica nanoparticles	The half-life of 9-Br-Nos-NLPs increased in the lungs compared with free drug powder after inhalation⁷³. Inhalation led to greater amounts of drugs and siRNA to be retained in the lungs than intravenous administration of the same formulation. Inhaled delivery also restricted the systemic uptake and accumulation of nanoparticles in other organs⁷⁵.
Paclitaxel	Lung surfactant mimetic and pH-responsive lipid nanovesicles	Fusogenicity of the nanoparticles enabled cytosolic delivery of paclitaxel to cancer cells but was non-toxic to normal cells. Inhaled delivery of drug-loaded nanoparticles led to lower drug concentrations in non-targeted sites (liver, spleen and plasma) compared with intravenous paclitaxel solution. Drug-loaded nanoparticles showed no lung toxicity⁹⁶.
Cisplatin	Sustained release lipid inhalation targeting (SLIT)	Inhaled cisplatin liposomes were well tolerated with no signs of systemic (nephrotoxicity, ototoxicity, or neurotoxicity) toxicity in lung cancer patients, which was attributed to a low systemic drug concentration. Side effects, including nausea, vomiting, dyspnea, fatigue and hoarseness, were observed¹²⁶.
9-Nitrocamptothecin	Liposomes	Inhaled 9-Nitrocamptothecin liposomes were safe and enabled disease stabilization in some lung cancer patients. The drug was also systemically absorbed following inhalation at high doses, leading to systemic side effects, including anemia, neutropenia and anorexia. A partial remission of liver metastasis was also observed in a patient with endometrial cancer, indicating the systemic potential of inhaled administration¹²⁷.