Cytotoxicity assessment of palbociclib-loaded chitosan-polypropylene glycol nano vehicles for cancer chemotherapy

The delivery of drugs in nanosized carriers arises as a very attractive solution. This study reports the in vitro cytotoxic effect of palbociclib loaded chitosan cross-linked polypropylene glycol nanocarriers. The nanocarriers were prepared by ion gelation using calcium chloride, calcium oxalate, and sodium tripolyphosphate as cross-linking agents. The influence of the cross-linking agent on the size and morphology of the chitosan- polypropylene glycol nanocarriers was studied by Dynamic Light Scattering (DLS), Scanning Electron Microscope (SEM), and Atomic Fluorescence Microscope (AFM). Tripolyphosphate assisted carriers was found higher amount palbociclib encapsulation capacity compared with other two carriers. The drug releasing behavior was studied at pH 6.8 which was based on the bulk erosion principal of the carriers. Palbociclib loaded chitosan-polypropylene glycol carriers were found to show excellent drug releasing kinetics and biocompatibility in in-vitro analysis. The unloaded chitosan-polypropylene glycol carrier was identified to have less inherent cytotoxicity, whereas the loaded carriers are as active as equal to pure palbociclib against the MCF-7 cancer cell line. The palbociclib loaded nanocarriers were studied to determine their potential anticancer activity against the MCF-7 cell line. The IC₅₀ values of three carriers chitosan-polypropylene glycol -I, chitosan-polypropylene glycol -II and chitosan-polypropylene glycol -III was observed 55.4, 51.0 and 38.7 mg/μL respectively. The effect of palbociclib uptake was evaluated by confocal microscopy using acridine orange/ethidium bromide and 4, 6-diamidino-2-phenylindole staining. Palbociclib loaded chitosan-polypropylene glycol nanocarriers show promise as potential candidates for cancer therapeutic applications.     

Development and validation of an UHPLC-MS/MS method for simultaneous determination of palbociclib,letrozole and its metabolite carbinol in rat plasma and pharmacokinetic study application

A sensitive and selective UHPLC-MS/MS method was developed and validated to simultaneously determine of palbociclib (PLB), letrozole (LTZ) and its metabolite carbinol (CBL) in rat plasma. After sample pre-treatment by acetonitrile-protein precipitation, the chromatographies resolution was performed using a reversed phase Acquity® UPLC BEH C18 column (1.7 μm particle size, 50 mm × 2.1 mm ID) in isocratic mobile phase consisted of a mixture of methanol and water containing 0.1% acetic acid (55:45, v/v) at pH 4.5. The flow rate and run time were 300 µL/min and 2.5 min, respectively. The target drugs were detected in multiple reaction monitoring (MRM) mode using tandem mass spectrometer coupled to a positive ESI interface to monitor the precursor-to-product ion transitions. Method validation was assessed as per the FDA guidelines for determination of PLB, LTZ and CBL within the concentration ranges 0.5–600 ng/mL for PLB and LTZ and 0.2–200 ng/mL for CBL (r² ≥ 0.997). The rest of validation parameters were within the accepted limits. The validated method was applied to PK study of these drugs in rats, and succeeded to determine the values of the PK parameters of PLB and LTZ.