Biological Transport of Nanoparticles

Submitted to:

Dr S.KananAssistant ProfessorCentre for Nanoscience and TechnologyPondicherry University

Submitted by:

Zaahir Salam

Drug DeliveryDrug delivery refers to approaches, formulations, technologies, and

systems for transporting a pharmaceutical compound in the body asneeded to safely achieve its desired therapeutic effect.

Most of the sites are accessible through either microcirculation byblood capillaries or pores present at various surfaces and membranes.

Most of the apertures, openings, and gates at cellular or subcellularlevels are of nanometer size. Hence, nanoparticles are the most suited toreach the subcellular level.

Prime requirements of any delivery system are:

ability to move around freely in available avenuescrossing various barriers that may come in the way.

Human body, the major passages are the blood vessels through whichmaterials 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 tocapillaries through branching and narrowing.

These capillaries go to the close vicinity of the individual cells. Afterreaching their thinnest sizes, the capillaries start merging with each otherto form the veins.

These veins then take the contents back to the heart for recirculation.

For any moiety to remain in the vasculature,

its one dimension narrower than the cross-sectional diameter ofthe narrowest capillaries, which is about 2000 nm.

For efficient transport the nanoparticle should be smaller than 300nm. But, just moving in the vessels does not serve the drug deliverypurpose. The delivery system must reach the site at the destinationlevel.

This requires crossing of the blood capillary wall to reach theextracellular fluid of the tissue and then again crossing of othercells, if they are in the way, and entering the target cell.

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

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 adherencejunctions are responsible for the development and stabilization of thetight junctions.

Different epithelial and endothelial barriers have different permeabilitiesmainly because of the differences in the structure and the presence oftight junctions.

While epithelia and brain capillary endothelium exhibit a high degree ofbarrier function, the vascular endothelium in other tissues has greaterpermeability. The tight junctions control the paracellular transport.

For example, diffusion of large molecules may not be feasible, butmigration of white cells is allowed.

As the nanoparticle based drug delivery is achieved by particletransport, it is important to understand the blood flow rates andvolumes of various organs and tissues.

Nanoparticles can have deep access to the human body because of theparticle 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 dailyfor 10 days at a dose of 1.25 mg/kg. The extent of absorption of the 50-nm particles was 34% and that of the 100-nm particles was 26%. Of thetotal absorption, about 7% (50 nm) and 4% (100 nm) were accounted forin the liver, spleen, blood, and bone marrow. Particles >100nm did notreach 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 bloodstreamcoupled with their high uptake by liver and spleen can be overcome byreducing the particle size, and by making the particle surface hydrophilicwith coatings, such as poloxamers or poloxamines.

Because of possible differences in particle uptake, gene expressionefficiencies can also be improved with smaller particles.

Doxorubicin Drug Delivery

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.