Development of Novel Drug Delivery System of Linezolid for Antitubercular Therapy

Abstract

The present study was aimed to develop and characterize novel linezolid (LNZ) loaded mannosylated gelatin nanoparticles (Mn-GNPs) using the Quality by Design (QbD) approach. The quality target product profile (QTPP) of the nanoparticulate formulation was defined and critical quality attributes (CQAs) were identified. The risk assessment and factor screening were done by Taguchi orthogonal array design to find out the most impacted factors affecting CQAs. A 33 Box-Behnken Design (BBD) was employed to further optimize the identified variables. The optimized LNZ loaded gelatin nanoparticles (GNPs) were then surface-functionalized with mannose (Mn-GNPs) for selective targeting to alveolar macrophages. The particle size of the GNPs and Mn-GNPs were found to be 235.3±11.3 nm with 0.127±0.02 polydispersity index (PDI) and 379 ± 21.7 nm with 0.148 ± 0.03 PDI, while the percent entrapment efficiency (%EE) was 56.8 ± 2.1% and 51.3 ± 3.6%, respectively. Moreover, an in-vitro drug release study was performed and has shown the sustained drug release from both the formulations. This was further confirmed by kinetic studies. The formulations were also screened for ex-vivo haemolytic toxicity study to ensure the in-vivo safety. The formulation was capable of sustained drug release above the MIC for more than 3-5 days with a significant increase in mean residence time (MRT) and the half-life of the drug. The present system is capable of reducing the dose, dosing frequency, and toxic adverse effects of the drug, which ultimately improves patient compliance and, therefore, a promising approach for the effective management of tuberculosis. newline