Cancers, Vol. 13, Pages 3700: Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes

Cancers, Vol. 13, Pages 3700: Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes Cancers doi: 10.3390/cancers13153700 Authors: Raghuram Kandimalla Farrukh Aqil Sara S. Alhakeem Jeyaprakash Jeyabalan Neha Tyagi Ashish Agrawal Jun Yan Wendy Spencer Subbarao Bondada Ramesh C. Gupta Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher yield of exosomes and could be loaded with higher amount of PAC compared to mature milk. Exosomal formulation of PAC (ExoPAC) showed higher antiproliferative activity and inhibition of colony formation against A549 cells compared with PAC alone, and also showed antiproliferative activity against a drug-resistant variant of A549. To further enhance its efficacy, exosomes were attached with a tumor-targeting ligand, folic acid (FA). FA-ExoPAC given orally showed significant inhibition (>50%) of subcutaneous tumor xenograft while similar doses of PAC sho...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research