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 SH2 domain of STAT3. In most of the studies, stattic has been proposed as a promising strategy for inhibition of STAT3 in cancer cells harboring constitutively active STAT3. However, lack of proper formulation due to the poor water solubility and low bioavailability of stattic is a major limitation for its usage in clinic. The aim of this project was to develop poly(ethylene glycole)-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, co-solvent evaporation method was used. Mean diameter and polydispersity index (PDI) of micelles were defined by light scattering method. Encapsulated drug levels were measured using high performance liquid chromatography (HPLC). Data were analyzed using Graph pad prism software through one-way ANOVA analysis of variance. 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 more than 6-fold increase in the water solubility of stattic (0.36 vs. 0.06 mg/mL). Respecting to high encapsulation efficiency, two micellar formulations were selected for further analysis that both of them released 70-80% of drug within the first hour, indicated burst release of drug. Conclusion: These findings show that PEG-b-PBCL copolymers can be a suitable vehicle for solubilization of stattic.