171: Nanoparticle Therapy in Lung Cancer

Introduction

Nanoparticles (NPs) are colloidal particles ranging in size from approximately 10 to 1000 nm in diameter and can be synthesized from a variety of materials (e.g., lipids, polymers, metals, and ceramics). Due to their unique properties, NPs have found increasing applications in medicine from drug delivery to imaging.

In the drug delivery arena, NPs are able to address many of the difficulties encountered during the administration of therapeutic compounds. The encapsulation of drugs within NPs can increase the solubility of insoluble drugs, improve pharmacokinetics through sustained release, alter biodistribution, protect sensitive drugs from low pH environments or enzymatic alteration, and, in some cases, provide targeting of the drug to the desired tissues.¹ Modern drug discovery and developmental technologies have yielded a wide array of small molecule and biologic drugs for the treatment of many diseases; however the requirements for these compounds to be successfully commercialized and translated into the clinic are challenging.

Cancer Treatment with Nanoparticles

Oncology is one field of medicine where NP-mediated drug delivery systems can potentially have a significant impact since issues with solubility and pharmacokinetics have limited the clinical application of many new, potentially effective anticancer drug candidates. There are several classes of promising NP drug delivery systems, including drug nanocrystals, liposomes, micelles, dendrimers, and polymeric NPs (Fig. 171-1).² Drug nanocrystals are simply pure drugs that have been processed down to nanometer sizes.³ The extremely small particle size increases the surface area of the drug, thereby increasing solubility. In contrast, liposomes are spherical lipid bilayers measuring a few nanometers in diameter.⁴ When used as a drug delivery vehicle, insoluble drugs can be transported within the hydrophobic environment of the lipid bilayer, whereas soluble drugs are contained within the internal aqueous compartment inside the liposome, thereby altering the pharmacokinetics and biodistribution of the native drug. Like liposomes, micelles are also composed of phospholipids. In aqueous solution, a micelle is formed by spontaneous self-assembly resulting in the exposure of the hydrophilic head regions to the surrounding solvent and aggregation of the hydrophobic tails at the micelle center. The core of the micelle can thereby contain small hydrophobic molecules such as therapeutic drugs, while remaining stable in aqueous solution. Dendrimers are highly branched molecules that can be used to deliver drugs via two different methods. Drugs can either be attached to the outer functional groups of the dendrimer branches, or encapsulated within the dendrimers to form a drug-dendrimer supermolecular assembly. Finally, polymeric NPs, which encapsulate drug within various polymers, tend to be more stable than liposomes and can increase the effective solubility of hydrophobic drugs. In addition, unlike liposomes, several polymeric systems appear to allow programmable, or at least controlled, drug release through the manipulation of the structure and composition of the polymer used to prepare the particles.^1,5,6