Nanoparticulation improves bioavailability of Erlotinib.

Objectives: Nanoparticulation using fat and supercritical fluid (NUFS (TM)) is a drug delivery platform technology enabling efficient and effective formulation of poorly soluble drugs. We performed experiments to examine whether NUFS could improve poor bioavailability and reduce fed-fasted bioavailability variances of erlotinib (Ert). Methods: NUFS-Ert was prepared using NUFS technology; its physical properties were characterized, and drug release was measured. Furthermore, in vitro and in vivo efficacy tests and pharmacokinetic analysis were performed. Results: NUFS-Ert nanoparticles had an average size of 250nm and were stable for 2 months at 40 degrees C, 4 degrees C, and room temperature. The dissolution rate of NUFS-Ert increased in bio-relevant dissolution media. NUFS-Ert was more potent in inhibiting EGF signaling and in suppressing the proliferation of A549, a human non-small cell lung cancer cell line. Furthermore, A549 xenografts in BALB/c nude mice treated with NUFS-Ert regressed more efficiently than those in the mice treated with vehicle or Tarceva (R). In addition, experimental lung metastasis was more efficiently inhibited by NUFS-Ert than by Tarceva (R). The relative bioavailability of NUFS-Ert compared with that of Tarceva (R) was 550% and the ratio of the area under the concentration-time curve (AUC) of fed state to the AUC of fasted state was 1.8 for NUFS-Ert and 5.8 for Tarceva (R). Conclusions: NUFS-Ert could improve poor bioavailability and reduce fed-fasted bioavailability variances of Ert. NUFS-Ert was more efficacious than Tarceva (R).