Novel Soluplus® nano-sized micelles for encapsulation of antineoplastic Paclitaxel: In vitro characterization

CAGEL M.; MORETTON M.A.; BERNABEU E.; GERGIC E.P.; LEGASPI M.J.; CHIAPPETTA D.A.

Cordoba

Congreso; RICIFA 2014; 2014

One of the most effective antineoplastic drugs used for the treatment of various solid tumors including ovarian cancer and metastatic breast cancers is paclitaxel (PTX), which is commercialized as a mixture of Cremophor EL® and dehydrated alcohol (1:1, v/v) (Taxol®) due to PTX hydrophobic nature and its low-aqueous solubility (0.3-0.5 μg/ml). However, seriously hypersensitivity reactions have been reported associated with the use of Cremophor EL®. Thereafter, the development of novel PTX formulations with enhanced drug aqueous solubility represents a technological challenge. In this framework, nanotechnology explores different strategies to improve apparent solubility and stability of poorly-soluble drugs. The present study investigates PTX encapsulation within nano-sized polymeric micelles employing the commercially available poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethyleneglycol) graft copolymer (Soluplus®) as micelle-former biomaterial. The aggregation behavior of the copolymer was characterized by the hydrophobic probe solubilization method where the critical micellar concentration was 0.55 x 10-4 %w/v at 25°C. Micelle hydrodynamic diameter (Soluplus® 10 %w/v) was 91.6±0.6 nm (PDI: 0.22) as determined by dynamic light scattering (DLS). Also the nanocarrier exhibited a spherical morphology as characterized by transmission electronic microscopy (TEM). In vitro solubility assays demonstrated that PTX was efficiently encapsulated within Soluplus® polymeric micelles where the drug apparent aqueous solubility was increased up to 11.34 mg/mL (polymer 10 %w/v). PTX encapsulation was also confirmed by nuclear magnetic resonance of hydrogen (NRMH). Moreover, the increment on PTX aqueous solubility (60,000-fold) is being reported for the first time for nano-sized polymeric carrier. Finally, this novel PTX micellar formulation represents an excellent nanotechnological platform to improve anticancer therapy. Further studies will be focused on PTX in vitro citotoxicity and in vivo oral bioavailability for drug-loaded micelles compared with commercially available Taxol®.