Surface functionalized albumin nanoparticles of palbociclib with amplified brain delivery for treating brain glioblastoma.

Glioblastoma multiforme (GBM) has a global occurrence of 0.59 to 3.69 per one lakh people. Palbociclib (Palbo), an inhibitor of CDK4 (cyclin dependent kinase) and CDK6, is used for treating cancer. Palbo showed a limited therapeutic effect in brains of transgenic mice after oral administration. Further, studies on P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) knock-out mice showed that P-gp and BCRP (efflux transporters) restrict Palbo's permeability across the blood-brain barrier (BBB). Hence, the clinical usefulness of Palbo for treating GBM is limited. Palbociclib-loaded nanoparticles of albumin (Nps-Bsa-Palbo) and palbociclib-loaded nanoparticles of albumin conjugated with Polysorbate 80 (Nps-Bsa-Palbo-Ps-80) were formulated and optimized using Design Expert 11.0.0. The Nps were prepared by desolvation with suitable size (195 nm and 221 nm) and zeta potential (13.4 mV and 10.6 mV). Nps-Bsa-Palbo and Nps-Bsa-Palbo-Ps-80 exhibited greater inhibition against the SH-SY5Y cell viability in comparison with free Palbo. Studies on healthy male rats confirmed that Nps-Bsa-Palbo-Ps-80 substantially enhanced Palbo distribution over free Palbo in the cerebellum, frontal cortex and posterior brain regions.