PURPOSE

This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX-GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin.

MATERIALS AND METHODS

DOX-GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake.

RESULTS

The optimized DOX-GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8±1.5 nm, the PDI of <0.3, the zeta potential of 28±2 mV, and the encapsulation efficiency of 80%±1.5%. Nanoformulation demonstrated a sustained release pattern over 48 h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX-GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX-GCPQ against RD cells as compared to DOX and blank GCPQ (<0.05). DOX-GCPQ exhibited low IC (1.7±0.404 µmol) when compared to that of DOX (3.0±0.968 µmol). In skin tumor xenografts, optical imaging revealed significantly lower DOX-GCPQ in heart and liver (<0.05) and accumulated mainly in tumor (<0.05) as compared to other tissues.

CONCLUSION

The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX-GCPQ an efficient nanotheranostic system.