Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS Method

Abstract

Celastrol (CL), a compound isolated from Tripterygium wilfordii, possesses various bioactivities such as antitumor, anti-inflammatory and anti-obesity effects. In previous studies, we developed CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with satisfactory formulation properties and in vitro cancer cytotoxicity effect. For further in vivo oral bioavailability evaluation, in this study, a simple and reliable LC-MS/MS method was optimized and validated to determine CL concentration in rat plasma. The separation of CL was performed on a C18 column (150 by 2 mm, 5 µm) following sample preparation using liquid–liquid extraction with the optimized extraction solvent of tert-butyl methylether. The assay exhibited a good linearity in the concentration range of 0.5–500 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/mL. The method was validated to meet the requirements for bioassay with accuracy of 91.1–110.0%, precision (RSD%) less than 9.1%, extraction recovery of 63.5–74.7% and matrix effect of 87.3–101.2%. The developed method was successfully applied to the oral bioavailability evaluation of CL-SFNP. The pharmacokinetic results indicated the AUC0-∞ values of CL were both significantly (p < 0.05) higher than those for pure CL after intravenous (IV) or oral (PO) administration of equivalent CL in rats. The oral absolute bioavailability (F, %) of CL significantly (p < 0.05) increased from 3.14% for pure CL to 7.56% for CL-SFNP after dosage normalization. This study provides valuable information for future CL product development.

microRNAs associated with the quality of follicular fluids affect oocyte and early embryonic development

“…Supplementation of the culture medium with FF or FF‐derived EVs changes the gene expression profiles of oviductal epithelial cells. 17 These reports indicate that the FF flux into the oviduct regulates the cells surrounding the embryos. Consistently, the protein expression of oviductal fluids (OFs) ipsilateral to the ovulated ovary differs from those of the contralateral counterparts.…”

Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability

“…To improve the bioavailability of Tri, a variety of oral nano-vehicles have been explored, including phytosomes [ 20 , 38 ], silk fibroin nanoparticles [ 39 ], and lactosylated albumin nanoparticles [ 40 ]. Compared with silk fibroin nanoparticles and lactosylated albumin nanoparticles, the selenized PLN system developed by us resulted in higher blood drug concentrations, in addition to longer in vivo residence times.…”

Surface-Modified Inhaled Microparticle-Encapsulated Celastrol for Enhanced Efficacy in Malignant Pleural Mesothelioma

“…Conventional routes of administration, such as oral and intravenous, are not ideal for Cela delivery. For instance, a pharmacokinetic study done on rats demonstrated the mean oral absolute bioavailability after oral administration (3 mg/kg) was very low at 3.14% [ 55 ]. Even though bioavailability is not a concern in intravenous administration, Cela is associated with many side effects, including infertility, cardiotoxicity, hepatotoxicity, hematopoietic system toxicity, and nephrotoxicity [ 38 ].…”