Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study

Abstract

Silibinin (SB) is shown to have an anticancer properties. However, its clinical therapeutic effects have been restricted due to its low water solubility and poor absorption after oral administration. The aim of this study was to develop SB-loaded PCL/Pluronic F68 nanoparticles for pulmonary delivery in the treatment of lung cancer. A modified solvent displacement process was used to make nanoparticles, which were then lyophilized to make inhalation powder, Nanoparticles were characterized with DSC, FTIR,SEM and In vitro release study. Further, a validated HPLC method was developed to investigate the Biodistribution study, pharmacokinetic parameters. Poly Caprolactone PCL / Pluronic F68 NPs showed the sustained release effect up to 48 h with an emitted (Mass median Aerodynamic diameter)MMAD and (Geometric size distribution)GSD were found to be 4.235 ±0.124 and 1.958±1.23 respectively. More specifically, the SB Loaded PCL/Pluronic F 68 NPs demonstrated long circulation and successful lung tumor-targeting potential due to their cancer-targeting capabilities. SB Loaded PCL/Pluronic F68 NPs significantly inhibited tumour growth in lung cancer-induced rats after inhalable administration. In a pharmacokinetics study, PCL/ Pluronic F68 NPs substantially improved SB bioavailability, with a more than 4-fold rise in AUC when compared to IV administration. These findings indicate that SB-loaded PCL/PluronicF68 nanoparticles may be a successful lung cancer therapy delivery system.

Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery

“…The freeze-dryer (LSFD1SU, Delvac Pumps Pvt. Ltd., Chennai, India) was set at −40 °C for 72 h. Detailed procedures were performed as per methods described in Patel et al 26,27 Defining the Quality Target Product Profile and Critical Quality Attributes. A number of patient-centered quality characteristics (QA) were found to satisfy the QTPP, including physical properties of drugs such as particle size, entrapment, and cumulative drug release after 24 h. Biopharmaceutical Performance, it is imperative to understand which of these can potentially be the critical quality attributes (CQAs) of nanoparticle formulations.…”

“…%EE was calculated by centrifugation of the aqueous phase to determine the free drug concentration. % EE was measured as per the method described in Patel et al , The % EE was calculated using the following eq . % 0.25em entrapment efficiency = ( total amount of drug − free amount of drug total amount of drug ) × 100 …”

“…Procedures were performed as per the method described in Patel et al The percent respirable fraction (RF) was calculated as mentioned below in eq 4. 26 Transform Infrared (FTIR) Spectroscopy. The IR spectra of compounds such as silibinin, chitosan, and folic acidconjugated nanoparticles were recorded using FTIR spectroscopy (CARY 630, Agilent Technologies).…”

“…DSC analysis of the samples was performed on a DSC 60 (Shimadzu, Tokyo, Japan) precalibrated for temperature and heat flux accurately using indium. DSC analysis of the samples such as silibinin, chitosan, and folic acid-conjugated nanoparticles was performed as per the method described in Patel et al 26,38 Scanning Electron Microscopy (SEM). SEM (JEOL-JSM-6380LVERDA) was used to examine the form and surface morphology of the optimized folic acid-conjugated CSNPs.…”

Recent Advances in Engineering Bioinks for 3D Bioprinting

“…[ 136 ] In addition, PCL is commonly used for printing bone, [ 137 ] blood vessel, [ 138 ] skin, [ 139 ] cartilage, [ 140 ] and nerve [ 141 ] tissues and for developing drug delivery systems. [ 142 ] However, PCL is poorly soluble in water and cannot be used to encapsulate cells.…”