Cellulose-based drug carriers for cancer therapy: Cytotoxic evaluation in cancer and healthy cells

Conventional chemotherapy drugs show lack of specificity, inducing reduced activity on the cancer treatment. They exhibit high toxicity and after a prolonged period of administration the cancer cells develop resistance (multiple-drug resistance, MDR). This situation leads to increasing the side effects of drugs and affect the quality of the patients' life. In order to overcome the above mentioned problems, the recent research community is focused primarily on developing smart drug delivery systems which respond in different stimulus, in the range of nanometer [1-3]. The objective of this work is the biological evaluation of synthesized double- layer microspheres based on cellulose coating, for delivery of chemotherapeutic drugs with low water-solubility. In a previous published work, we have designed double-layer microspheres, based on the co-polymerization of widely-used sensitive polymers (Methyl acrylic acid and N-isopropylacrylamide) and modified cellose's coating. Briefly, we have synthesized and fully characterized Poly(methyl acrylic acid-co-N-isopropylacrylamide-co-ethyleneglycol dimethacrylate)@cellulose succinate (P(MAA-co-NIPAAM-co-EGDMA)@CS) microspheres by a combination of sol-gel method, distillation precipitation co-polymerization and chemical deposition. The resulting spheres were characterized structural through spectroscopy as well as morphological. The anticancer agent daunorubicin was encapsulated in the spheres, and drug's release behavior was evaluated at acidic and slightly basic pH conditions. The highlight of the previous evaluation is the microspheres' response at acidic pH environment for targeted release of the drug at the tumor affected area in contrary to neutral pH. This fact was a sign that our system may be a potential drug delivery vehicle for cancer treatment, as it is well known that tumor's environment is acidic. For that purpose we evaluated the cytotoxic effects of spheres, spheres loaded with daunorubicin and free daunorubicin via MTT assay in MCF-7 (breast cancer) and HeLa cells (cervical cancer) as a function of concentration and in different time intervals. Finally, HEK 293 (Human Embryonic Kidney) cells were incubated with unloaded microspheres in order to evaluate the cytotoxic activity in healthy cells. (C) 2014 Elsevier B.V. All rights reserved.