(T0930-09-55) Micellar Oligo(Lactic Acid)8-Doxorubicin Formulation Enhances Antitumor Efficacy and Reduces Toxicity in a TNBC Model Compared to Free Doxorubicin

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high systemic toxicity associated with conventional chemotherapies like Doxorubicin (Dox). This study evaluates the physicochemical properties, cytotoxicity, and in vivo efficacy of a novel PEG-assisted micellar formulation of OLA8-Doxorubicin (OLA8-Dox) compared to free Dox in a murine TNBC model.

Methods: OLA8-Dox was formulated into micelles using PEG4k-b-PLA2k copolymers. The formulation was characterized by particle size, polydispersity, drug loading, and colloidal stability. In vivo efficacy was evaluated using an orthotopic 4T1 TNBC model (n=5/group). Mice were treated with OLA8-Dox (10 mg/kg) or free Dox (5 mg/kg), and tumor volumes were monitored over 21 days. At endpoint, toxicity and metastatic spread were evaluated via histopathology of major organs.

Results: The PEG4k-b-PLA2k micelles encapsulating OLA8-Dox showed uniform particle size distribution (~30 nm), high drug-loading efficiency (97%), and good colloidal stability at 4 °C and room temperature for at least two weeks in aqueous medium. In vivo, OLA8-Dox reduced tumor volume by 92%, compared to 66% reduction with free Dox. No body weight changes were observed in the OLA8-Dox or saline-treated groups throughout the treatment period. OLA8-Dox-treated mice showed no signs of systemic toxicity or metastasis, while the free Dox group exhibited visible toxicity and metastatic spread to distant organs.

Conclusion: Micellar formulation of OLA8-Dox using PEG4k-b-PLA2k copolymers significantly improves therapeutic efficacy and safety over free Dox in TNBC models. These findings support further development of OLA8-Dox as a promising nanocarrier-based chemotherapeutic with reduced systemic toxicity and enhanced antitumor response.

References: Rasoulianboroujeni, M., Repp, L., Lee, H. J., & Kwon, G. S. (2022). Production of paclitaxel-loaded PEG-b-PLA micelles using PEG for drug loading and freeze-drying. Journal of Controlled Release, 350, 350-359.

Size distribution and aqueous stability of OLA8-Dox analyzed by DLS and HPLC

Body weight and tumor volume changes in a TNBC BALB/c mouse model