Development of polymeric nanoparticles loaded with STAT3 inhibitory, Stattic, for targeted cancer therapy

Background. STAT3 is an oncogenic signaling pathway found constitutively active in many types of human malignancies and plays a key role in cancer progression. Stattic is a small molecule, which selectively inhibits the SH2 domain of STAT3. In most studies, stattic has been proposed as a promising strategy STAT3 inhibition in cancer cells harboring constitutively active STAT3. However, the lack of proper formulation due to the poor water solubility and low bioavailability of stattic is a major limitation for its usage in the clinic. This project aimed to develop poly(ethylene glycol)-block-poly(caprolactone) (PEG-b-PCL)-based polymeric micelles loaded with stattic and evaluate drug encapsulation efficiency and release in the developed formulations.

Methods. In this experimental study, to prepare stattic loaded micellar formulations, the co-solvent evaporation method was used. The mean diameter and polydispersity index (PDI) of micelles were defined by the light scattering method. Encapsulated drug levels were measured using high-performance liquid chromatography (HPLC). Data were analyzed using GraphPad Prism software through one-way ANOVA.

Results. Stattic was loaded in the polymeric micelles with encapsulation efficiency ranging from 40% to 73%. Drug loaded micelles were measured between 90 to 130 nm in size. PDI was obtained 0.3-1, and encapsulation of stattic in Polyethylene glycol-block-poly (α-benzyl carboxylate ε-caprolactone (PEG-b-PBCL) micellar formulation resulted in a more than 6-fold increase in the water solubility of stattic (0.36 vs. 0.06 mg/mL). Regarding high encapsulation efficiency, two micellar formulations were selected for further analysis in that both of them released 70-80% of the drug within the first hour, indicating burst release of the drug.

Conclusion. These findings show that PEG-b-PBCL copolymers can be a suitable vehicle for the solubilization of stattic.