# Targeted Lipid-Based Drug Delivery Systems for Lung Cancer Therapy
## 2 Cancer
### Lung Cancer and Particle Deposition  
There are mainly two different types of lung cancer: the small cell lung cancer (SCLC) and the non-small cell lung cancer (NSCLC). NSCLC, being the most common, is responsible for 80-85% of the lung cancer cases [21]. SCLCs are acquired from the hormonal cells of the lung and are the most dedifferentiated cancers, and generally occur as central mediastinal tumours. SCLCs comprise 10-15% of all lung cancers, and they spread rapidly into submucosal lymphatic vessels and regional lymph nodes and are always present without a bronchial invasion. SCLCs remain one of the deadliest malignancies with a 5-year survival rate of less than 7% [22].  
NSCLC is further classified into three types: squamous-cell carcinoma, adenocarcinoma and large-cell carcinoma. Squamous-cell carcinoma comprises 25-30% of all lung cancer cases. It occurs from early versions of squamous cells that are present in the airway epithelial cells of bronchial tubes in the centre of the lungs. This subtype of NSCLC is mainly caused by smoking cigarettes. Adenocarcinoma is the most common type of lung cancer and comprises around 40% of all lung cancers [23]. Adenocarcinoma is the most prevalent type of lung cancer in both male and female smokers and non-smokers. It generally occurs in the periphery of the lungs and prevents the entry of large particles into the lungs. In comparison to other types of lung cancers, adenocarcinoma tends to grow slower and has a significant chance of being detected in the lungs before spreading to other parts of the body from the lungs. Large-cell (dedifferentiated) carcinoma generally accounts for 5-10% of lung cancers. The central part of the lungs is significantly affected by large-cell carcinoma, which sometimes extends into nearby lymph nodes, the chest wall and distant organs. Large-cell carcinoma tumours are strongly associated with smoking [24]. However, the identification of genetic changes in NSCLC and a better understanding of the composite biology of molecular subtypes of the disease has changed the diagnosis and treatment of advanced lung cancer [25]. Early screening of lung cancer is considered a significant step in improving patient survival [26].  
There are various therapies for lung cancer, including surgery, chemotherapy and radiotherapy, depending on the stage of the cancer [27]. During drug administration for pulmonary delivery, the deposition of drug particles in the different parts of the lung depends on the particles' size, shape and density. The right lung consists of three lobes and the left lung of two lobes. The lungs further comprise the bronchi and small airways, the alveoli, lymph tissues and blood vessels [28].  
There are three mechanisms by which particles can deposit in the lungs:  
* Inertial Impaction: The deposition of the particles near the surfaces of the airways during the air flow changes [29]. Most of the particles deposit at the oropharynx and the primary bronchi and this is usually observed for dry powder inhalers, metered dose inhalers and nebulisers with particle sizes larger than 5 \(\upmu\)m [28]. This may be responsible where particles fail in manoeuvrability and hence deposition occurs in the upper respiratory tract.
* Sedimentation: The deposition of the particles is highly affected by the breathing process and gravitational forces. Particles within the size range of 1 and 5 \(\upmu\)m deposit to the smaller airways and the bronchioles (secondary bronchi) [28].
* Brownian Diffusion: The deposition of the particles in areas where they can be dissolved in the alveolar fluid. Particles smaller than 1 \(\upmu\)m are deposited in the area of the lung and particles with a size less than 0.5 \(\upmu\)m are exhaled [28]. Deposition of formulation in this region can be further improved by holding breath for a few seconds.