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.