Controlled release of N-(2-hydroxyphenyl)-2-propylpentanamide nanoencapsulated in polymeric micelles of P123 and F127 tested as anti-proliferative agents in MDA-MB-231 cells

The compound N-(2-hydroxyphenyl)-2-propylpentanamide, named HO-AAVPA, has better antiproliferative properties against MDA-MB-231 cells than its parent compound, valproic acid (VPA). However, the low water solubility of HO-AAVPA can reduce its therapeutic effectiveness. An alternative to this problem is to use polymeric micelles of triblock copolymers, such as poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEOa-PPOb-PEOa; a = 20, b = 70 (P123); a = 100, b = 65 (F127)), which can help to increase the water solubility of the drug and improve its biodistribution. In this work, the physicochemical properties of the complexes formed between the polymeric micelles and drug (F127 + HO-AAVPA, P123 + HO-AAVPA) were studied. The water solubility of HO-AAVPA increased by 31-fold in P123 micelles and 23-fold in F127 micelles. The hydrodynamic diameter (D-h) of P123 and F127 drug-charged micelles remained stable at approximately 30 nm between 22 and 60 degrees C. The polymeric micelle-drug interaction was studied using differential scanning calorimetry (DSC), which found that the aggregate enthalpy (Delta H-agg ) decreased with the presence of HO-AAVPA. The in vitro release profiles of both systems were adjusted to a Weibull's pharmacokinetic model, indicating that the drug released in a sustained manner. Lastly, (P123 + HO-AAVPA) and (F127 + HO-AAVPA) in the MDAMB-231 cell line showed anti-proliferative properties. With the obtained results, we conclude that polymeric micelles increase the solubility of HO-AAVPA to form stable aggregates and that both the P123 and F127 systems have similar physicochemical properties that can harbor and release HO-AAVPA while maintaining its biological reported effects.