Arun Kumar, Shreedevi (2021-07). Engineering Drug Delivery Platforms for Cancer and Infectious Diseases. Doctoral Dissertation. Thesis uri icon


  • Vaccines and chemotherapeutic agents have been developed to treat infectious diseases and cancer, respectively. However, efficacy of the therapeutic agents used to treat these diseases can be significantly improved through the use of drug delivery platforms. Although, polymer-based drug delivery platforms have been developed, owing to technical challenges, these platforms often do not get clinically translated. In this dissertation, three polymer-based platforms were engineered: 1) injectable polyester-based platform for on-demand therapeutic delivery, 2) molybdenum disulfide (MoS2)-incorporated polyacrylonitrile (PAN) nanofibers with improved cytocompatibility, and 3) doxorubicin (DOX)/ polyvinyl alcohol (PVA)-loaded shape memory polymer (SMP) foams for increased drug loading. Firstly, single injection vaccines (SIV) platforms provide exciting opportunities for efficient vaccine delivery. However, current platforms do not cater cargo versatility or delayed burst release kinetics that is crucial for optimal immune response. Thus, an injectable polyester-based platform called "polybubbles" was developed to maintain functionality of therapeutic agents housed within while enabling delayed burst release of cargo. This platform also enables on-demand delivery capabilities upon extracorporeal activation through the incorporation of near-infrared (NIR)-sensitive gold nanorods (AuNRs). Secondly, PAN nanofibers can be used as bioscaffolds to enable effective chemotherapy release. However, cytocompatibility of the PAN nanofibers would have to be improved for clinical translation. Thus, defect-rich MoS2 nanoassemblies were incorporated into PAN nanofibers through electrospinning. Ideal defect morphology was identified and was successfully used to improve mechanical properties and hydrophilicity of PAN nanofibers. Increased cell adhesion and viability was observed with the incorporation of defect-rich MoS2 indicating improved cytocompatibility. These hybrid nanofiber scaffolds thus show potential for downstream biomedical applications including drug delivery. Lastly, SMP foams can be used as a small molecule carrier, specifically for anti-cancer applications. DOX-loaded SMP foams can thus potentially be used as an adjuvant to breast cancer tumor resection while precise sealing of the post-surgical void. DOX loading onto the SMP foams was improved successfully using viscosity modulating agent called PVA. This modified drug formulation did not have significant impact on the properties of SMP or DOX functionality in vitro. Study of these three platforms thus establish the clinical potential of polymer-based materials in improving therapeutic efficacy.

publication date

  • July 2021