Subacute tissue biodistribution of magnetic nanoparticles functionalized with chitosan intended for drug delivery systems.

AGOTEGARAY M; AZCONA P; ZYSLER R; CAMPELO ADRI¨¢N; MASSHEIMER VIRGINIA; GUMILAR F; MINETTI A; LASSALLE V

ROSARIO

Congreso; 8¡ã Congreso Latinoamericano de Órganos artificiales, Biomateriales e Ingenier¨ªa de Tejidos; 2014

Nanoparticles are described as materials with three external equal nanoscale dimensions. Magnetic  nanoparticles (MNPs) present the special characteristic associated to the feasibility of external manipulation under the influence of an external magnetic field. An interesting and promising application lies in the use of MNPs as drug targeted delivery systems by directing the drug to the desired part of the body. This would avoid side effects associated to the free form of the drug, increasing circulation times and reducing toxicity. Two magnetic nanodevices intended for targeted drug delivery systems were evaluated in mice to study their tissue distribution after a subacute exposure. Formulations consist in a magnetic core composed by magnetite functionalized with oleic acid and recovered with crosslinked and non-crosslinked chitosan (N1 and N2, respectively). N1 and N2 were intraperitoneal administered once a week for four weeks. A control group was administered with saline solution (n = 8 per group). Doses employed were about 33 mg MNPs/kg. Then animals were sacrificed by cervical dislocation and the organs such as liver, spleen, kidneys, lungs, brain and heart were analyzed by VSM (Vibrating Sample Magnetometry) to determine the content of the MNPs by magnetism measurements avoiding the physiological contribution of endogenous iron. The care and the handling of the animals were in accordance with the internationally accepted standard Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the National Institute of Health and CICUAE (Comit¨¦ Institucional para el Cuidado y Uso de Animales de Experimentaci¨®n ¨C Universidad Nacional del Sur). Results. Results expressed as Mean ¡À S.E.M (standard error of mean) found for the biodistribution of N1 and N2 are presented in the following table: TISSUE  N1 (¦Ìg / g of tissue ) ¡À S.E.M. N2 (¦Ìg / g of tissue) Spleen                 690 ¡À 149  1208 ¡À 200 Liver 137 ¡À 74  400 ¡À 200 Heart 37 ¡À 4  30 ¡À 4 Lung 117 ¡À 62  55 ¡À 13 Kidney 22 ¡À 6 27 ¡À 11 Brain 26 ¡À 8  16 ¡À 1 Discussion. Biodistribution study after a subacute exposure to N1 and N2 revealed that spleen is the organ where the greatest amount of nanoparticles is located. Similar quantities of MNPs were found for both formulations related to heart, kidney and brain. In the case of brain, a very small quantity was distributed taking into account the impermeability of the blood-brain barrier. Significant differences were observed for liver and lung between N1 and N2. This finding could be ascribed to differences in the subacute metabolism of both nanodevices. Conclusion.  Data related to the biodistribution of the MNPs are crucial to the knowledge of their behavior in vivo in order to better understand their potential interactions with physiological components. This information is of most importance regarding to the effective implementation of these systems as drug delivery devices. Further studies related to toxicity as well as culture cell assays are being developed in order to whole characterize the biological properties of these MNPs intended for biomedical applications.