Formulation development of albumin based theragnostic nanoparticles as a potential delivery system for tumor targeting

Background: Generally, chemotherapeutic drugs attack on both normal and tumor cells non-specifically causing life threatening side effects, necessitating targeted drug delivery to tumors. Purpose: The purpose of this study is to formulate albumin-based nanoparticles for tumor targeted drug delivery and noninvasive diagnosis. Methods: Albumin based nanoparticles (NPs) were developed as a potential tumor theragnostic agent by entrapping an anti cancer drug, doxorubicin and a near infrared dye, indocyanine green. Theragnostic nanoparticles were prepared using a well established coacervation/nanoprecipitation method followed by lyophilization. The formulation was optimized by varying process parameters using full factorial design of experiments. Release of dye and drug from NPs and physical state of the drug in NPs was studied using DSC. The NPs were injected into tumor bearing mice intravenously and imaged using a bio-imager. Results: The optimized nanoparticle formulation had a particle size of 125.0 +/- 1.8 nm, poly dispersity index of 0.180 +/- 0.057 and zeta potential of -32.7 +/- 0.9 mV. The release of dye and drug from the nanoparticles was determined to be quasi-fickian diffusion mediated. Differential scanning calorimetry (DSC) studies revealed the stability of drug in the NP. The in-vivo studies showed enhanced accumulation of the dye loaded NPs at the tumor site than the dye solution, thus allowing noninvasive tumor monitoring. Conclusion: These results project the newly proposed and evaluated nanoparticle formulation as a potential tumor targeting and imaging delivery system.