Development and Optimization of Methotrexate Encapsulated Polymeric Nanocarrier by Ionic Gelation Method and its Evaluations

Abstract

Methotrexate encapsulated nanocarriers (M-CNCs) were synthesized via the ionic gelation method and using Taguchi design to optimize the formulation for; size, percent entrapment efficiency (%EE), and percent drug loading (%DL). The M-CNCs are designed to improve therapeutic efficacy and minimize the side effect of Methotrexate. Various critical factors, such as pH, polymer to a cross-linker ratio (v/v), and reaction time (h), are considered to investigate their influence on the selected responses during the optimization. The physicochemical properties and morphology of the optimized M-CNCs were investigated by Dynamic light scattering, Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction, Thermogravimetric analysis, and High-resolution transmission electron microscopy. Further, In-vitro release, stability, pharmacokinetics, and toxicity were studied. The FTIR result revealed the cross-linking between the drug and polymer. The nanocarrier was found to be stable with spherical morphology and crystalline nature. Optimized formulation shows, Zavg=155 nm, EE=87 %, and D=49 %. The In-vitro drug release showed a controlled release profile of MTX up to 72 h. Pharmacokinetic evaluation of M-CNCs in healthy Sprague Dawley rats showed an improvement in plasma drug concentration. Toxicity evaluation by the histology study revealed a healthy organ architecture and the absence of pathological lesions. Overall, the formulated M-CNCs showed enhanced bioavailability with no toxicity. © 2022 Wiley-VCH GmbH.