Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS
Shuyu Zhan1,2, Amy Paik2, Felicia Onyeabor2
1Department of Pharmacy, College of Medicine, Jiaxing University, Jiaxing 314001, China.
Molecules (Basel, Switzerland)
|August 1, 2020
Summary
Celastrol (CL) silk fibroin nanoparticles significantly enhance oral bioavailability in rats. A validated LC-MS/MS method confirmed increased CL concentrations, aiding future product development.
Area of Science:
- Pharmacology and Drug Delivery
- Analytical Chemistry
- Biomaterials Science
Background:
- Celastrol (CL), derived from Tripterygium wilfordii, exhibits potent antitumor, anti-inflammatory, and anti-obesity properties.
- Previous research established CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with favorable in vitro anticancer activity.
- The need for in vivo oral bioavailability assessment of CL-SFNP prompted the development of a robust analytical method.
Purpose of the Study:
- To develop and validate a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying Celastrol (CL) in rat plasma.
- To evaluate the in vivo oral bioavailability of CL-SFNP compared to pure CL in rats.
- To provide data supporting the potential of CL-SFNP for improved therapeutic applications.
Main Methods:
- Optimization and validation of an LC-MS/MS assay using a C18 column and liquid-liquid extraction with tert-butyl methylether for CL quantification in rat plasma.
- Assay validation included linearity (0.5-500 ng/mL), lower limit of quantification (LLOQ) of 0.5 ng/mL, accuracy (91.1-110.0%), precision (<9.1% RSD), extraction recovery (63.5-74.7%), and matrix effect (87.3-101.2%).
- Pharmacokinetic studies involving intravenous (IV) and oral (PO) administration of CL and CL-SFNP in rats, with plasma CL concentrations determined by the validated LC-MS/MS method.
Main Results:
- The developed LC-MS/MS method demonstrated excellent linearity, accuracy, precision, and reliability for CL quantification in rat plasma.
- Pharmacokinetic analysis revealed significantly higher area under the curve (AUC0-∞) for CL from CL-SFNP compared to pure CL after both IV and PO administration (p < 0.05).
- Oral absolute bioavailability (F) of CL significantly increased from 3.14% for pure CL to 7.56% for CL-SFNP (p < 0.05) after dosage normalization.
Conclusions:
- A validated LC-MS/MS method provides a reliable tool for assessing CL pharmacokinetics in vivo.
- CL-SFNP significantly enhances the oral bioavailability of Celastrol in rats compared to the free compound.
- These findings highlight the therapeutic potential of CL-SFNP and offer valuable insights for future Celastrol product development.
