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Biological transport of nanoparticles

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Biological transport of Nano particles. with emphasis on Drug delivery

Biological transport of Nano particles. with emphasis on Drug delivery

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  • 1. Biological Transport of Nanoparticles Submitted to: Dr S.Kanan Assistant Professor Centre for Nanoscience and Technology Pondicherry University Submitted by: Zaahir Salam
  • 2. Drug Delivery Drug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. Most of the sites are accessible through either microcirculation by blood capillaries or pores present at various surfaces and membranes. Most of the apertures, openings, and gates at cellular or subcellular levels are of nanometer size. Hence, nanoparticles are the most suited to reach the subcellular level.
  • 3.  Prime requirements of any delivery system are: ability to move around freely in available avenues crossing various barriers that may come in the way.  Human body, the major passages are the blood vessels through which materials are transported in the body.  The blood vessels are not left in any organ as an open outlet of the pipe, rather they become thinner and thinner and are finally converted to capillaries through branching and narrowing.  These capillaries go to the close vicinity of the individual cells. After reaching their thinnest sizes, the capillaries start merging with each other to form the veins.  These veins then take the contents back to the heart for recirculation.
  • 4.  For any moiety to remain in the vasculature, its one dimension narrower than the cross-sectional diameter of the narrowest capillaries, which is about 2000 nm.  For efficient transport the nanoparticle should be smaller than 300 nm. But, just moving in the vessels does not serve the drug delivery purpose. The delivery system must reach the site at the destination level.  This requires crossing of the blood capillary wall to reach the extracellular fluid of the tissue and then again crossing of other cells, if they are in the way, and entering the target cell.
  • 5. There are two routes for crossing the blood capillaries and other cell layers, 1.Transcellular 2.Paracellular Transcellular route, the particulate system has to enter the cell from one side and exit the cell from the other side to reach the tissue. The particulate system has to survive the intracellular environment to reach the target tissue. Paracellular route. the particulate system is not required to enter the cell; instead, it moves between the cells
  • 6. Paracellular route: Paracellular movement of moieties including ions, larger molecules, and leukocytes is controlled by the cytoskeletal association of tight junctions and the adherence junctions called apical junction complex.  While tight junctions act as a regulated barrier, the adherence junctions are responsible for the development and stabilization of the tight junctions.
  • 7. Different epithelial and endothelial barriers have different permeabilities mainly because of the differences in the structure and the presence of tight junctions. While epithelia and brain capillary endothelium exhibit a high degree of barrier function, the vascular endothelium in other tissues has greater permeability. The tight junctions control the paracellular transport. For example, diffusion of large molecules may not be feasible, but migration of white cells is allowed.
  • 8. As the nanoparticle based drug delivery is achieved by particle transport, it is important to understand the blood flow rates and volumes of various organs and tissues.
  • 9. Nanoparticles can have deep access to the human body because of the particle size and control of surface properties Experiments by Jani et al. have elegantly demonstrated the size effect. Polystyrene particles in the size range 50–3000nm were fed to rats daily for 10 days at a dose of 1.25 mg/kg. The extent of absorption of the 50nm particles was 34% and that of the 100-nm particles was 26%. Of the total absorption, about 7% (50 nm) and 4% (100 nm) were accounted for in the liver, spleen, blood, and bone marrow. Particles >100nm did not reach the bone marrow, and those >300nm were absent from the blood. Particles were absent in the heart or the lung tissue. The rapid clearance of circulating particles from the bloodstream coupled with their high uptake by liver and spleen can be overcome by reducing the particle size, and by making the particle surface hydrophilic with coatings, such as poloxamers or poloxamines. Because of possible differences in particle uptake, gene expression efficiencies can also be improved with smaller particles.
  • 10. Doxorubicin Drug Delivery
  • 11. CONCLUSIONS • Nanoparticles offer unique properties as compared to micro or macroparticles. Salient features include the following:  Small size.  High surface area.  Easy to suspend in liquids.  Deep access to cells and organelles.  Variable optical and magnetic properties.  Particles smaller than 200nm can be easily sterilized by filtration with a 0.22-mm filter. Drugs, being mostly organic compounds, are more sticky in nature as compared to inorganic materials, such as silica or metal oxides. Hence, it is harder to make smaller nanoparticles of drugs compared with hard materials. Drug nanoparticles can be produced either by milling of macroparticles or by fast precipitation from solutions.

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