Oral chemotherapeutic delivery system developed using PCL from PolySciTech

Paclitaxel is a widely applicable anticancer agent which prevents cancer cells from dividing and proliferating. Currently, the only administration route for paclitaxel is by intravenous injection. For chronic applications, this can be a very invasive procedure, such as surgical placement of a PICC line in the vein of the arm or port-a-cath directly into the entrance of the heart. Clearly, an oral delivery system would be preferred in terms of patience comfort as well as management of costs and potential complications associated with catheters.  By itself, Paclitaxel has very poor uptake when administered orally. However, researchers have utilized PCL (PolyVivo AP129) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) and conjugated it to chitosan to form a biocompatible micelle system which significantly enhances paclitaxel absorption. This research holds promise for less-invasive and more sustainable delivery of paclitaxel to patients. Read more: Almeida, Andreia, Daniella Silva, Virginia Gonçalves, and Bruno Sarmento. “Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery.” Drug Delivery and Translational Research (2017): 1-11. http://link.springer.com/article/10.1007/s13346-017-0357-8

“Abstract: In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents. Keywords: Chitosan, Polycaprolactone, Paclitaxel, Micelles, Drug delivery”

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