Fabrication and evaluation of self-assembled folic acid surface modified Nintedanib mixed micelles to treat Idiopathic Pulmonary Fibrosis

The objective of this study is to prepare and characterize Nintedanib (NTB)-loaded folic acid (FA)- conjugated mixed micelles (MMs) (FA-NTB-MMs) to treat Idiopathic Pulmonary Fibrosis (IPF). The critical micelle concentration of the excipients used was determined by the dynamic light scattering method. The MMs were prepared using the thin film hydration method. The optimized MMs were conjugated with FA. MMs were characterized for particle size, zeta potential, PDI, surface morphology, entrapment efficiency, solid-state characterization by X-ray diffraction studies, differential scanning calorimetry, Fourier transform infrared spectroscopy, and in vitro drug release. The optimized MMs produced a particle size of 100.80 ± 0.60 nm, PDI 0.22 ± 0.01, zeta potential −14.30 ± 2.21 mV and encapsulation efficiency of 89.85 ± 3.71 %. Transmission Electron Microscopy (TEM) images showed a uniform spherical shape and size. The solid-state characterization results confirmed the presence of NTB in the MMs. The drug release was 98.66 ± 3.99 % in seven days, indicating sustained drug release. In vivo studies were performed to evaluate the pharmacokinetic behaviour and pharmacodynamics of the developed formulation. The surface-modified MMs with FA exhibited a better pharmacokinetic profile than pure NTB and showed improved pharmacodynamic profiles in the oropharyngeal bleomycin-induced IPF model. Thus, the developed FA-NTB-MMs could be further tested for IPF treatment.