Synthesis and Characterization of Gel Microparticles for Lung Cancer Delivery

Abstract

Drug delivery through the use of hydrogel biomaterials has received a considerable amount of progress over the past decade especially for pharmacological purposes like lung cancer treatment. However, substantial challenges for effective treatment remain, including targeting and controlled release. The design of the human lung provides a unique filter system that allows large particles in the venous blood stream to get trapped in capillary beds near the lungs. Gel microparticles (GMPs) designed for the delivery of therapeutic drugs through this mechanism are formed through a Michael-Addition reaction using polyethylene glycol (PEG) and dithiothereitol (DTT). In this thesis, we investigate the characteristics of PEG based hydrogels by varying the PEG concentration and molecular weight of the polymer in order to define a relationship between the rate of degradation and the crosslink density within the gel. The degradation of 10K PEG took 14 days compared to the 1K PEG hydrogel that showed a higher storage modulus (G’) and took 40 days to degrade. Increasing the PEG concentration from 20wt% to 40wt% for the 1K PEG showed an increase from 41.3kPa ± 13.2 to 171.9kPa ± 0.04, which revealed a direct linear relationship between the concentration and G’. In order to develop a method for measuring the effective G’ of GMPs, G’ comparisons were made between bulk gels and a GMP paste. The results showed that we can estimate the G’ of the GMP to be within a factor of 2 from the G’ of the bulk gels. The GMP synthesis process was optimized to shearing a W/O emulsion at 2000s-1 for 20min., which reproducibly generated uniform, homogenous GMPs with a 3-4μm diameter. Drug-loaded encapsulated nanoparticles (NPs) were implemented to improve the GMP’s control over the drug release rates. The effect of NPs on GMP droplet formation was analyzed and showed that particle breakup is affected by the NP stabilizers. Using the capillary number a relationship was determined between the molecular weight of the NP stabilizer and the surface tension within the GMP. These results can be utilized to produce ideal particles for effective therapeutic delivery for lung cancer treatment.