Biological transport of Nano particles. with emphasis on Drug delivery

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.