Evaluation of lapatinib ditosylate nanoparticles for enhanced dissolution rate, oral bioavailability and effective oral carcinoma treatment

Lapatinib ditosylate (LD) is a chemotherapeutic agent that belongs to Class II of the Biopharmaceutical Classification System. The objective of this work was to enhance oral bioavailability of LD by developing a nanoparticle solid dispersion. Lapatinib ditosylate nanoparticles (LDNP) were prepared by a combination of precipitation followed by high pressure homogenization. The optimized LDNP formulation, containing LD, hydroxypropyl methyl cellulose acetate succinate, Brij-35, and sodium lauryl sulfate in the ratio of 1:4:0.5:0.2, was found to provide an average particle size of 103 ± 4.6 nm after freeze drying. Scanning electron microscopy and solid-state characterization revealed rounded particles in an amorphous state. Nanonization significantly (<i>p</i> < 0.05) increased dissolution rate (90 ± 4.6% within 30 min) compared with the physical mixture (29 ± 1.3% in 30 min). Pharmacokinetic evaluations performed in Wistar rats showed 1.3- and 1.4-fold increase in <i>C</i>_max and AUC_total after LDNP administration compared with commercial formulation. LDNP demonstrated similar growth inhibition in oral carcinoma MOC2 and FaDu cells as that of LD solution. LDNP showed complete remission of xenografted oral cancer in a C57BL/6 mouse model after seven doses of 100 mg/kg LDNP. The LDNP formulation can be developed to enhance the oral bioavailability of LD for effective oral cancer treatment.