Investigation on preparation and characterization of protein drug loaded nanoparticles and their biological effects

اسدالهی, ابرا هیم and اسدي, دکتر اسداله and زهري, دكتر صابر and برزگر, دكتر ابوالفضل (2011) Investigation on preparation and characterization of protein drug loaded nanoparticles and their biological effects. Masters thesis, University of Mohaghegh Ardabili.

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Abstract

Improvements in biotechnological industries lead to production of many novel protein and peptide drugs which potentially applicable in treatment of many diseases like cancer, disease which are resulted from defect in lysosomal and digestive enzymes, thrombolytic disease and diabetes. The use of these therapeutic agents is restricted by instability and low biological half-life, solubility and cell membrane impermeability. By the use of nanoparticles overcoming these limitations is possible and engulfment of therapeutic agents by nanoparticles result in 1-drug molecules be unrecognizable by immune system, 2-increase in the size of therapeutic agents and slower remove by renal filtration, 3-increase in apparent solubility and decrease in precipitation of poor soluble drugs in blood vessels, 4- effective intracellular delivery and endosomal escape of therapeutic molecules. Other advantages which are result from the use of drug delivery systems are possibility of passive and active targeting. In this work, triblock copolymers were synthesized and after confirmation of their synthesis by FTIR and H-NMR spectroscopy, biocompatibility tests were performed. Electron microscopy studies verified formation of micelles by copolymers and their CMC were determined. Also fluorescence microscopy studies showed that these nanoparticles were able to enter the cells. Loading of peptide drug agents (iturin, surfactin and gramicidin) on nanoparticles were confirmed by CD, fluorescence, FTIR, and electron microscopy studies. HeLa cancerous cell line was treated with iturin in free form and then was loaded on nanoparticles. In addition, LNCaP cancerous cell line was treated by surfactin and gramicidin loaded nanoparticles and their effects on cells were measured and compared to free surfactin and gramicidin effects. Results showed that these therapeutic agents when loaded on nanoparticles have more effect on cells in compared to their free form (in the case of surfactin and gramicidin the observed changes in toxicity is significant). According to the obtained results, we suggest that BDP16 and BDP18 have good biocompatibility and essential features for formulation and use as effective peptide drugs nanocarrier.

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