Nanocarriers targeting the diseases of the pancreas.

Diseases of the pancreas include acute and chronic pancreatitis, exocrine pancreatic insufficiency, diabetes and pancreatic cancer. These pathologies can be difficult to treat due to the innate properties of the pancreas, its structure and localization. The need for effective targeting of the pancreatic tissue by means of nanoparticles delivering therapeutics is a major focus area covered and discussed in this review. Most common diseases of the pancreas do not have specific and direct medical treatment option, and existing treatment options are generally aimed at relieving symptoms. Diabetes has different treatment options for different subtypes based on insulin having stability problems and requiring injections reducing patient compliance. Pancreatic cancer progresses silently and can only be diagnosed in advanced stages. Therefore, survival rate of patients is very low. Gemcitabine and FOLFIRINOX treatment regimens, the most commonly used clinical standard treatments, are generally insufficient due to the chemoresistance that develops in cancer cells and also various side effects. Therefore new treatment options for pancreatic cancer are also under focus. Overcoming drug resistance and pancreatic targeting can be achieved with active and passive targeting methods, and a more effective and safer treatment regimen can be provided at lower drug doses. This review covers the current literature and clinical trials concerning pancreatic drug delivery systems in the nanoscale focusing on the challenges and opportunities provided by these smart delivery systems.

Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver.

Erlotinib (ERL), a tyrosine kinase inhibitor approved for therapeutic use in non-small cell lung cancer is further researched for eventual liver cancer treatment. However, conventional ERL has important bioavailability problems resulting from oral administration, poor solubility and gastrointestinal degradation into inactive metabolites. Alternative administration routes and nanoparticulate drug delivery systems are studied to prevent or reduce these drawbacks. In this study, ERL-loaded CD nanosphere and nanocapsule formulations capable of cholesterol depletion in resistant cancer cells were evaluated for ERL delivery. Drug loading and release profile depended largely on the surface charge of nanoparticles. Antiproliferative activity data obtained from 2D and 3D cell culture models demonstrated that polycationic ßCD nanocapsules were the most effective formulation for ERL delivery to lung and liver cancer cells. 3D tumour tumoral penetration studies further revealed that nanocapsule formulations penetrated deeper into the tumour through the multilayered cells. Furthermore, all formulations were able to extract membrane cholesterol from lung and liver cancer cell lines, indicating the induction of apoptosis and overcoming drug resistance. In conclusion, given their tumoral penetration and cell membrane cholesterol depletion abilities, amphiphilic CD nanocapsules emerge as promising alternatives to improve the safety and efficiency of ERL treatment of both liver and lung tumours.