DRUG DELIVERY AND DIAGNOSTIC

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.For example protein and peptide drugs have to be delivered by

injection(daily life) or a nanoneedle Diagnosis is the identification of the nature and cause of a certain

phenomenon.

WHY NANOTECHNOLOGY IN DRUG DELIVERY AND DIAGNOSTIC ?

• (i)Targeting, to increase the drug concentration at desired sites of action and reduce systemic levels of the drug and its toxic effects in healthy tissues.

• (ii)Improved solubility• (iii)Constant rate of drug delivery, resulting in

zero-order release kinetics to maintain a constant therapeutic dose at the site of action .

• (iv)Increased drug stability, to reduce degradation and maximize drug action.

• (vi)Drug delivery across the blood–brain barrier (BBB).

NANOMATERIALS USED IN DRUG DELIVERY AND DAGNOSTIC

• NANOPORES • FULLERENES • NANOPARTICLES • DENDRIMERS • LIPOSOMES • NANOSHELLS • NANOROBOTS• Nanosensor • Gold particles • Quantum dots• Nanotechnology on chip (biochip, protein chips)

NANOPORES• These are surface perforated with holes

and in nano dimensions . for example, be created by a pore-forming protein or as a hole in synthetic materials such as silicon or graphene.

• Desai and his co workers fabricated tiny chambers si wafer in which biological cell can be placed .

• Small molecules like oxygen, glucose and insulin can pass through these pores but large molecules such as Ig’s and graft borne virus particles cannot pass and this process is called immunoisolation .

FULLERENES

• A fullerene is any molecule composed entirely of carbon, Spherical fullerenes are also called buckyballs . Fullerenes are similar in structure to graphite, which is composed of stacked graphene sheets of linked hexagonal rings; but they may also contain pentagonal rings.

• C60(type of fullerene) is commonly used in drug delivery due to its good bio compatibility and low toxicity.

• Against several diseases like parkison’s and HIV .

FULLERENES DERIVATIVES

• ANTI VIRAL AGENTS for eg USED IN HIV • Anti cancerous • Antioxidants.

NANOPARTICLES

• A nanoparticle are sub micron sized polymeric colloidal particle with a therapeutic agent of interest encapsulated within their polymeric matrix or adsorbed or conjugated on to the surface

• Highly versatile system ,overcome physiological barriers and guide the drugs to specific cells .control release pattern of drug and drug level for long time.

• Anticancer drug loaded nanoparticles are mainly concentrated in kuffer cells in liver .

DENDRIMERS• These are spherical polymeric molecules

formed through nanoscale hierarchical Self assembly process. These are the macromolecule, which is characterized by its highly branched 3D structure that provides a high degree of surface functionality and versatility. Dendrimers have been refered to as the “Polymers of the 21st century.

LIPOSOMES • Liposomes are spherical self-closed

structures , composed of lipid bilayers , which enclose part of the surrounding solvent into their interior.

• Can incorporate both hydrophobic and hydrophilic drugs in them.

• Liposomes are used in the diagnostic imaging by using contrast agent .

• Lipoplexes are the nanostructure(net positive charge) which have the cationic liposomes with polyanionic plasmid DNA .it is used in the gene targeting to liver .

NANOSHELLS

Nanoshell is a type of spherical nanoparticle consisting of a dielectric core which is covered by a thin metallic shell usually gold coated silica .

These are used for early detection of cancer and its treatment by embedding drug containing tumor targeted hydrogel polymer and injected in the body .which when heated with laser (infrared)and thus release drug at tumor site .

NANOROBOTS• Nanorobotics is the emerging technology

field creating machines or robots whose components are at or close to the scale of a nanometer (10−9 meters).

• Nanorobots can be used in the biomedical field .

• Nature already provides nanorobots in human body for e.g .lymphocytes ,fibroblasts ,neutrophils etc

• Nanorobotics will allow doctors to perfrom direct in vivo surgery on individual human cell.

• Its exterior shape consists of diamondoid material, to which may be attached an artificial glycocalyx surface that minimizes fibrinogen adsorption and bio activity ensuring sufficient biocompatibility to avoid immune system attack.

DRUG TARGETING

• Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others and reducing the side effects.

• Two approaches are –passive and active targeting • In Passive drug targeting accumulation of drug is at

particular site due to physicochemical or pharmacological factors.

• In active drug targeting employs specific modifications of drug/drug carrier nanoystems with active agents having selective affinity for recognizing and interacting with a specific cell,tissue or organ in the body .

NANOSENSORS• Nanosensors with immobilized bioreceptors

probes that are selective for target analyte molecules are nanobiosensors. they integrated into other technologies such as lab-on-chip or biochips /protein chips.

• PEBBLE NANOSENSOR (probes encapsulated by biological localised embedding ) Probes Encapsulated By Biologically Localized Embedding (PEBBLEs) are isolated nanoscale devices for intracellular chemical analysis. This schematic shows a generalized view of an ideal PEBBLE with many options for encapsulated constituents. In the examples that follow, it will become clear how this technology allows us to probe the nanoscale chemical and biological world.PEBBLE sizes can range from 20 to 200 nm in diameter.

• It is used in early detection of cancer .• Optical biosensors used in diagnostic by

using surface plasmon resonance technology

• Surface plasmon resonance technology(SPR)• It is an optical electrical phenomenon involving the

interaction of light with the electrons of the metal• Photon of light transfer its energy to group of

electrons(plasmon)at the surface of metal• ELECTRONIC NANOBIOSENSORS – It works by

electronically detecting the binding of a target DNA molecule to a sensor on a microchip.

Principle of immunoassays:Principle of immunoassays:

• Reactions between two protein molecules Reactions between two protein molecules can be extremely specific.can be extremely specific.• One type of molecule (antibody) can be One type of molecule (antibody) can be immobilised on gold sensor surface.immobilised on gold sensor surface.• The second (antigen) will bind changing The second (antigen) will bind changing the refractive index .the refractive index .• This change is detected by changed This change is detected by changed angle of surface plasmon resonance.angle of surface plasmon resonance.

NANOPARTICLE TECHNOLOGIES

• GOLD PARTICLE• NANOBARCODES• QUANTUM DOTS• NANOPARTICLE PROBES• MAGNETIC NANOPARTICLES

GOLD PARTICLES• Gold nanoparticles are attached onto DNA or

an antibody or other molecule instead of flurosencent molecule which assemble on a sensor surface only in the presence of a complementary target

• These are particularly good labels for sensors because a variety of analytical techniques

can be used to detect them, optical absorption, fluroscence ,raman scattering,

atomic and magnetic force.• This can be use to detect microorganism and

could replace pCR and flouroscent tag. Raman active dyes are attach on to DNA which attach to gold nano particle. Since

raman band is narrower than the floroscence band it allowa more dyes to detect more

targets quickly .these particles easily prepared ,they have very low toxicity.

NANOBARCODES• Submicrometer metallic barcodes with

striping patterns prepared by sequential electrochemical deposition of metal ions. These particles make them useful for bioanalytical measurements.

• The differential reflectivity of adjacent stripes enables identification of the striping patterns by conventional light microscopy.

• Biobarcode assays are an ultra senstive method for detecting proteins analytes relies on magnetic microparticle probes with Ab that specifically bind the target of interest and nano particle probes that are encoded with DNA that is unique to protein target of interest and Ab .

QUANTUM DOTS• A quantum dot is a nanocrystal made of

semiconductor materials that glow when excited by a light source at any wavelength from infrared to visible to ultraviolet.

• They can be specifically attached to biological materials such as cells , proteins and nucleic acids making them powerful tagging agents.

• Advantages of QD technology are :-high sensitivity

-availability of IR/red colours enables whole blood assays

-fluorescence is stable -highly resistant to degradation• Major challenge is that QDs have an oily

surface.• Used for diagnose genotyping ,white blood

assays, multiplexed diagnostics

MAGNETIC NANOPARTICLES• Magnetic nanoparticle are a class of nanoparticles

which can be manipulated using magnetic field. Such particles commonly consist of magnetic elements such as iron, nickel and cobalt and their chemical compounds.

• They can be used to label specific molecule, structures ,m/o’s .these labelled magnetic nanoparticles get changed their magnetic field when come in contact with the analyte and which is detected by sensitive magnetometer .

• these can be used for the detection of circulating cancer cell in the blood and isolation of m/o’s such as bacteria useful for curing serious infection.

• Ferrofluid consists of magnetic core surrounded by polymeric layer coated with antibodies for capturing cells .they are colloidals when mix with the sample containing target cells ,Ab conjugated to the magnetic core bind the Ag associated with the target cells

• For eg used for the telomerase activity in the biological sample ,MRI

NANOTECHNOLOGIES IN DRUG DELIVERY AND DIAGNOSTICS

• AFM(ATOMIC FROCE MICROSCOPY)• CANTILEVERS ARRAYS • SPR(SURFACE PLASMON RESONANCE )• SERRS ( SURFACE ENHANCED RESONANT

RAMAN SPECTROSCOPY )• RESONANCE LIGHT SCATTERING TECHNOLOGY

ATOMIC FORCE MICROSCOPY • AFM is used for diagnostic and

cytogenetics investigation of biochemical and structural properties of human chromosomes

• AFM have been used to obtain information from chromosomal probes. the final resolution allows a more precise localization compared to standard techniques ,and the extraction of very small amounts of chromosomal DNA by scanning probe is possible.

CANTILEVERS ARRAYS DEVELOPED BY concentris •These are the small beams used to screen biological samples for the presence of particular genetic SEQ. the surface of each cantilever is coated with DNA that can bind to one particular target seq•On exposure of the sample to beams ,the surface stress bends the beams by appx 10 nm to indicate that the beams have found the target in the sample.the surface stress results in minute deflections of the cantilevers and these deflections correlated directly to the conc of the target substance•Used for the detection of disease by breath analysis e.g presence of acetone,dimethylamine . •It requires no labels ,optical excitation ,external probes and is rapid ,highly specific ,sensitive and portable.

APPLICATION OF NANODIAGNOSTICS

• Use of nanocrystals in immunohistochemistry • Glucose monitoring in vivo by nanosensors• Detection of disease biomarkers • Detection of single nucleotide polymorphisms• Detection of disease genes • Detection of microrganisms such as

bacteria ,viruses • Treatment of diseases such as cancer ,eye

problems, joints problems etc .