468054 Preparation of a Drug Delivery System (DDS) of Hydropylic and Hydrophobic Drugs: In Vitro Validation in Human Lung Cancer Cells

Thursday, November 17, 2016: 10:30 AM
Continental 5 (Hilton San Francisco Union Square)
Fernando Mesías-Recamán1, Jesus Rodriguez-Rodriguez2, Miguel A. Galán3 and Eva Martín del Valle3, (1)Chemical engineering, University of Salamanca, Salamanca, Spain, (2)University of Salamanca, (3)Department of Chemical Engineering, University of Salamanca, Salamanca, Spain

PREPARATION OF A DRUG DELIVERY SYSTEM (DDS) OF HYDROPYLIC AND HYDROPHOBIC DRUGS: IN VITRO VALIDATION IN HUMAN LUNG CANCER CELLS

Fernando Mesías-Recamán, Jesús A. Rodríguez-Rodríguez, Miguel A. Galán, Eva Martin Del Valle

It is well known that current therapies present many side effects due to their low tumor cells-recognition capacity (low specificity), low solubility, low specificity, low bioavailability, prolonged circulation time in the body (1, 2) and high toxicity (3). In this regard, developing new medical strategies which could solve these disadvantages is necessary. Therefore, in this work, two different drugs with different hydrophobicity were combined to obtain an important synergic effect on the tumor cell line H460 (human lung cancer).

Our strategy is based on the combination of the carboxymethyl-β-cyclodextrin (CMCD) covalently attached to cisplatin as paclitaxel (PTX) carrier. In this manner, cisplatin and PTX could be delivered at the same time obtaining a synergic effect. CMCD was selected due to it presents low toxicity, small size, non-immunogenicity, excellent biocompatibility and high conjugation capacity with a variety of lipophilic compounds (4, 5, 6).

Furthermore, this molecule presents a hydrophilic ring and a hydrophobic cavity (7) that allows the link of cisplatin in its surface and forms the inclusion complexes with PTX. Cisplatin was covalently attached to the outside oligosaccharide ring through activation of the carboxylate functional groups of the CMCD, while PTX was included inside the oligosaccharide ring forming an inclusion complex. In addition, the solubility of both drugs was increased in aqueous conditions when drugs were bind to/formed the inclusion complex with CMCD.

This system was characterized by NRM and FTIR, and thermodynamic studies. The PTX inclusion was determined by HPLC.

Later, their stability over time and the paclitaxel and cisplatin release kinetics were also studied. Finally, the efficacy of the both drugs delivery system has been validated in vitro with the H460 cell line by MTT assays and promising results have been obtained. Thus, this system could be a novel strategy to avoid the side effects that current antitumor therapies generate.

 

References

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