Design of pH-responsive polymeric nanocarrier for targeted delivery of pyrogallol with enhanced antitumor potential in colon cancer

Abstract

PurposeTo synthesize a polymeric pH-sensitive nanocarrier for the delivery of pyrogallol and investigate the anti-tumor activity of pyrogallol-loaded polymeric nanogel against colon cancer in rats. MethodsPoly(ethylene glycol)/polyacrylic acid (PEG/PAAc) nanogel was performed using gamma irradiation technique at irradiation doses; 30,40, and 50 kGy. The particle size distribution and diameter were investigated under the influence of various parameters by using dynamic light scattering analysis (DLS). The particle size was diminished by increasing AAc content and irradiation dose. Characterization of the performed nanogel was performed by (FT-IR) and (TEM). In vitro drug release behavior of the nanogel towards pyrogallol drug was assessed. Furthermore, the anti-cancer therapeutic efficiency of pyrogallol loaded PEG/PAAc nanogel was evaluated in a chemically induced colon cancer model in rats. ResultsPyrogallol/PEG/PAAc significantly reduced tumor incidence and volume as compared to DMH group. Also, it activated apoptotic pathway via up-regulating Bax, cytochrome C, cleaved caspase-3, p53, and down-regulating Bcl-2 expression. Furthermore, it attenuated cell cycle progression via reducing Cyclin A, Cyclin D1, and Cyclin E expression. It exhibited anti-proliferative activity through inhibiting PI3K/AKT signaling and downregulating the phosphorylation of AKT. It reduced pro-inflammatory cytokines TNF-α and IL-6. Results were confirmed by histopathological examination of colonic tissue. Interestingly, pyrogallol/PEG/PAAc demonstrated anti-tumor potential more efficiently than free pyrogallol, revealing localized drug delivery. ConclusionThis formulation could be considered as a promising agent in the treatment of colon cancer.