Category: Formulation and Quality
Purpose: The goal of this project is to improve the oral bioavailability of fenretinide by loading the drug in exosomes purified from bovine milk.
Methods: Fenretinide, a synthetic retinoid derivative, is useful in treating neuroblastoma and other forms of cancer. Its usefulness is limited due to its poor aqueous solubility and bioavailability. To overcome these limitations, the drug was loaded in exosomes purified from pasteurized bovine dairy milk. The exosomes were isolated using a sequential ultra-centrifugation process. The size distribution and purity of the exosomes were determined using nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) imaging. An ultrasonic passive loading process was used to load fenretinide in the exosomes. The effect of sonication time on drug loading was studied. The intestinal permeability of drug from the exosomes was determined using Caco-2 transport analysis.
Results: The ultracentrifugation process effectively produced pure exosomes with an average size of 141.7 ± 0.6 nm. TEM imaging confirmed uniform particle size distribution without the presence of larger vesicles. In addition, these exosomes could be lyophilized for redispersion upon use. Maximum drug loading (8.12% ±0.18) was achieved using 15 min of sonication. Extending sonication time to 60 min resulted in a decrease in drug loading. In vitro permeability studies showed that the mean apparent permeability of drug-loaded exosomes through Caco-2 cells was (1.85 ± 0.5) × 10-5 cm/sec, compared to (8.8 ± 0.5) × 10-8 cm/sec for pure drug.
Conclusion: Exosomes purified from bovine dairy milk have been previously shown to be of low toxicity and could be used as a means for improving the bioavailability of fenretinide. These exosomes could be obtained in large amounts using an easy and economical process.