Mechanism of Nitroimidazole Coated Magnetic Nanoparticles Embedded in Micro-organisms as Delivery Systems

摘要

Avirulent Bacteria and parasites act as "tiny missile like carriers" capable to carry the magnetic nanoparticles (NMP) together with anticancer or radiosensitizer drugs at the tumor site. We compared the iron-oxide particles binding characteristics with nitroimidazole in monoaxenic avirulent E.histolytica NIH 200, Candida albicans and Salmonella BR 509 alongwith their membrane lipids and drug sensitivity. Major results were: 1. Microscopic experiments showed engulfed MNP particles passaged across the microbe membrane; 2.E.histolytica was oval shaped; Candida was thread like structure with capability of iron and manganese synthesis in situ; and Salmonella BR 509 was rod shaped 1 micron in size; 3. The nano-sized particles were diffused slowly into the cell membrane by stimulation of colony stimulating factor; 4.The nitroimidazole coated nanoparticles embedded in microbe membranes showed sequential reduction of gluconeogenesis and energy metabolic integrity loss in microbes due to their interaction with host tissue sites; 5.The MNP-loaded micro-organism showed slow drug delivery rate from micro-organisms dependent on size of nanoparticle, composition of microorganism membrane; 6. The comparison showed the nitroimidazole release rate was dependent on medium pH, temperature, nutrients used and colony stimulating factor in Candida > Salmonella > E.histolytica at temperature range of 41.5to 42.5 ℃ and magnetic field at 0.5-1 MHz;7. At high magnetic field, the microorganism cells showed necrosi s, loss of cell viability. In conclusion, the mechanism of nitroimidazole controlled release across microbial membrane depends on physiological pH, culture medium composition, nanoparticle size, colony stimulating factor, magnetic field and temperature. The mechanism of controlled drug delivery by avirulent micro-organisms has significance in designing a targeted anticancer drug therapy to focal tumors.