Formulation and characterization of erlotinib-loaded nanolipidic carriers and its application as dry powder inhaler

Abstract

NSCLC is usually irresponsive to therapy. However 10-35% of NSCLC patients have a sensitizing mutation in EGFR gene, which makes them sensitive to the EGFR inhibitors. Of these inhibitors, erlotinib is currently the mainstream treatment modality in advanced and/or metastatic NSCLC which is also available as an oral tablet.

Aims The purpose of this study was to prepare an erlotinib-loaded SLN formulation for developing a DPI for direct delivery of erlotinib to lung NSCLC tumors.

Materials and Methods Several SLN formulations were prepared using hot homogenization method. SLNs were characterized with regard to size, morphology. The SLN formulation parameters were optimized to reach desirable encapsulation and loading efficiency. The cytotoxicity of the erlotinib-loaded SLNs in comparison with free erlotinib was assessed using MTT assay in A549 cell line. Finally, SLNs were spray dried to produce mannitol-containing microparticles to fulfill the requirements for optimal pulmonary delivery. The flowability of powder was calculated by Hausner ratio and Carr Index. Aerodynamic behavior of the microparticles was evaluated using the Next Generation Impactor (NGI).

Results Optimal compritol/poloxamer 407 SLNs were produced in sub-100 nm and spherical shape, which showed an encapsulation efficiency of 78.21% for erlotinib. MTT assay showed that the SLN formulation enhanced the cytotoxicity of erlotinib in A549 cell line, while the unloaded SLNs were biocompatible. The SLNs were successfully spray dried into microparticles with mannitol as a carrier. The powder showed suitable flowability and aerodynamic behaviors, as assessed by Carr Index, Hausner ratio and NGI results.

Discussion The optimal compritol/poloxamer 407 SLNs had a favorable size and encapsulation efficiency and enhanced the cytotoxicity of erlotinib in A549 cells. The spray dried microparticles exhibited acceptable flowability and aerodynamic behavior and could thus provide a deep inhalation pattern, holding promise for applications in local delivery of erlotinib to pulmonary tumors.