• Save
Nanoparticle
Upcoming SlideShare
Loading in...5
×
 

Nanoparticle

on

  • 2,448 views

 

Statistics

Views

Total Views
2,448
Views on SlideShare
2,445
Embed Views
3

Actions

Likes
8
Downloads
0
Comments
13

1 Embed 3

http://www.linkedin.com 3

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel

110 of 13 Post a comment

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…

110 of 13

Post Comment
Edit your comment

    Nanoparticle Nanoparticle Presentation Transcript

    • GANDHI SONAM M.1ST M.PHARMINDUSTRIAL PHARMACYSUBJECT TEACHER :MR.SATEESHA S.B
    • What is Nanotechnology? Nanotechnology is the act of purposefully manipulating matter at the atomic scale, otherwise known as the "nanoscale." In Pharmacy its all about synthesizing, characterizing and screening the particle at Nano range.
    • Therapeutic Introduction application of Nanoparticles Various methods Surface engineering of preparation of Nanoparticles In Vivo fate and Pharmaceutical Biodistribution of aspects of Nanoparticles Nanoparticles3/18/2013 4
    • Introduction Targeted drug delivery implies for selective and effectivelocalization of pharmacologically active moiety atpreidentified targets in therapeutic concentration, whilerestricting its access to non-target normal cellular linings,thus minimizing toxic effects and maximizing therapeuticindex The colloidal carriers based on biodegradable andbiocompatible polymeric systems like liposomes,nanoparticles and micro emulsion have largely influencedthe controlled and targeted drug delivery concepts
    • Nanoparticle dimensions between 1 nm and 1000 nm Nano derives from the Greek word "nanos", which means dwarf or extremely small. It can be used as a prefix for any unit to mean a billionth of that unit. A nanometer is a billionth of a meter or 10-9 m.3/18/2013 6
    •  Nanoparticles are solid colloidal particles ranging from 1 to 1000 nm in size, they consist of macromolecular materials in which the active ingredients (drug or biologically active material) is dissolved, entrapped, or encapsulated, or adsorbed.3/18/2013 7
    • Definition Nanocapsules: in which the drug isconfined to an aqueous or oily coresurrounded by a shell-like wall.Alternatively, the drug can be covalentlyattached to the surface or into the matrix
    • Nanoparticles Nanospheres Nanocapsules Matrix type Membrane wall structure in structure with an which a drug is oil core containing dispersed drug3/18/2013 9
    • 3/18/2013 10
    • 3/18/2013 11
    • ADVANTAGES: Nanoparticle drug carriers have higher stabilities Nanoparticles have higher carrier capacity Feasibility of incorporation of both hydrophilic and hydrophobic substances Feasibility of variable routes of administration Nanoparticles are biodegradable, non-toxic and capable of being stored for longer periods. nanoparticles can also be used for controlled delivery of drugs Nanoparticles reduces dosing frequency and have higher
    • Disadvantages of nanoparticles Polymeric nanoparticles posses limited drug-loading capacity On repeated administration, toxic metabolites may be formed during the biotransformation of polymeric carriers.The polymeric nanoparticles are relatively slowly biodegradable which might cause systemic toxicity.
    • Polymers for nanoparticles Natural hydrophilic polymers Proteins: - Gelatin, albumin, lectins, legumin. Polysaccharides: - alginate, dextran, chitosan, agarose. Synthetic hydrophobic polymersPre-polymerized polymers: - Poly (e-caprolactone) (PECL),Poly (Lactic acid)(PLA), PolystyrenePolymerized in process polymers: - Poly (isobutyl cyanoacrylates) (PICA), Poly (butyl cyano acrylates)
    • Preparation of nanoparticles: Nanoparticle Preparation Using Polymerization Based Methods The polymers used in this are poly methyl methacrylate, polyacrylamide, polybutyl cyanoacrylate.,etc Two approaches adopted for preparation of nanoparticles using polymerization technique are1. Methods in which the monomer to be polymerized is emulsified in a non-solvent phase(emulsion polymerization)2. Methods in which the monomer is dissolved in a solvent for the resulting polymer (dispersion polymerization)
    • Methods used for nanoparticle preparation Methods used for nanoparticle preparation are1. Emulsion polymerization2. Dispersion polymerization3. Interfacial polymerization4. Interfacial complexation
    • 1. EMULSION POLYMERIZATION:The process can be Conventional – continuous phase is aqueous i.e., o/w emulsion Inverse – continuous phase is organic i.e., w/o emulsion.Two mechanisms of emulsion polymerization areA. Micellar nucleation and polymerizationB. Homogenous nucleation and polymerization
    • A. Micellar nucleation and polymerization In this the monomer is emulsified in non-solvent phase using surfactant moleculesThis leads to the formation ofi. Monomer- swollen micelleii. Stabilized monomer droplet• Monomer swollen micelle have sizes in nanometric range and have much larger surface area compared to monomer droplet• Polymerization reaction proceeds through nucleation and propagation stage in presence of chemical or physical initiator.
    • CONTINUE…… Energy provided by initiator creates free monomers in continuous phase, which then collide with surrounding unrelative monomers and initiate polymerization chain reaction. The monomer molecule reaches the micelle by diffusion from the monomer droplets through continuous phase, thus allowing polymerization to progress within micelles. Here monomer droplets act as reservoirs of monomers.
    • Surfactant Monomer droplet Drug Monomer Monomer supply Monomer supply for growth CatalystMonomer bearing Stabilized polymericmicelle Nucleated micelle nanospheres3/18/2013 20
    • B. Homogenous nucleation and polymerization In this method monomer is sufficiently soluble in continuous outer phase. Nucleation and polymerization can directly occur in this phase leading to formation of primary chains called oligomers. In this both micelle and droplets act as monomers reservoir throughout polymer chain length. When oligomers reach certain length, they precipitate and form primary particles and stabilized by surfactant molecules provided by micelle and droplets in which the drug will entrapped to form nanoparticles.
    • Surfactant Drug Monomer Monomer dropletActivated Monomer Oligomer Primary Stabilized polymeric particle nanospheres 3/18/2013 22
    • . DISPERSION POLYMERIZATION In emulsion polymerization, monomer is emulsified in non-solvent phase by means of surfactants. In case of dispersion polymerization, monomer is dissolved on aqueous medium. The nucleation is directly induced in aqueous monomer solution and presence of stabilizer or surfactant is not necessary for formulation of stable nanospheres.
    • CONTINUE……… This method is used to prepare biodegradable polyacrylamide and polymethyl-methacrylate (PMMA) nanoparticles. Being very slowly biodegradable and biocompatible, PMMA nanoparticles have been considered as optimal polymeric systems for vaccination purpose.
    • 3. INTERFACIAL POLYMERIZATION In this method, a polymer that becomes core of nano- particle and drug molecule to be loaded is dissolved in volatile solvent. Solution is then placed in to a non-solvent for both polymer and core phase Polymer phase is separated at o/w interphase. Resultant mixture instantly turns to milky owing to formulation of nanocapsules.
    • PREPARATION OF NANOPARTICLES BYINTERFACIAL POLYMERIZATION :Core phase + drug Polymer phase Core dispersed in polymer phase -- - - - - - - - - - - -- - - - - - - - - - - (O/W emulsion) Non-solvent, which precipitate out polymer from either of phases Nanocapsules ( 30-300 nm ) 3/18/2013 26
    • CONTINUE……… Size of nanocapsules is 30-300 nm Drug loading depends on drug solubility in core phase Surfactant can be added to stabilize dispersion. Example: encapsulation of proteins, enzymes, antibiotics.etc.,
    • PHARMACEUTICAL ASPECTS OFNANOPARTICLES:  From pharmaceutical point of view nanoparticles prepared should be free from toxic impurities, should be easy to store and administer and should be sterile if parenterally used. Three parameters performed before releasing them for clinical trials are  Purification  Freeze drying  Sterilization
    • Purification of nanoparticlesCommonly used methods are Gel filtration Dialysis Ultra-centrifugation Cross flow filtration A new cross – flow filtration method is used for purification of nanoparticles in industrial point of view. In this method nanoparticle suspension is filtered through membranes, with the direction of fluid being tangential to the surface of the membrane. As a result clogging of filters is avoided.
    •  CONTINUE…….. The suspension is subjected to several filtration cycles, while the filtrate is discarded containing soluble impurities. This leads to the concentration of suspension. After this, water is added to maintain the volume of circulation constant. This is a simple and can be done at a faster rate. Purification of large amounts of nanoparticles can be done without alteration in the sizes.
    • Cross-flow filtration technique:NanopraticlesImpuritesMembrane3/18/2013 31
    • Gel filtration : Remark :Nanoparticle High molecular weight substances and impurities Impurity are difficult to remove Schematic principle 3/18/2013 32
    • 3/18/2013 33
    • Dialysis : Remark : • High molecular weight impurities are difficult to remove •Time consuming process3/18/2013 34
    • Freeze drying of nanoparticles: This involves freezing of the nanoparticles and subsequent sublimation of its water content under reduced pressure to get a free flowing powdered material. Advantages: Prevention from degradation and solubilization of polymer. Prevention from drug leakage, drug desorption . Easy to handle and store and helps in long term preservation. Readily dispersed in water without modifications in their physicochemical properties. Prevention from drug leakage Disadvantage: Nanocapsules having an oily core surrounded by polymer wall tend to agglomerate. This can be overcome by dessicating in lyoprotective agent ex:
    • Sterilization of nanoparticles: Nanoparticles intended for parenteral use should be sterilized to be pyrogen free before using on animals or humans. Sterilization is achieved by using aseptic technique throughout preparation, processing and formulation or by autoclaving or using γ- irradiation. Autoclaving and γ- irradiation show impact on the physicochemical properties of the particles with modification of particle size stability and drug release characteristics. Sterilization is a critical step and should be systematically investigated during formulation development stage.
    • Characterization of nanoparticles:1. Size and morphology2. Specific surface3. Surface charge and electrophoretic mobility4. Surface hydrophobicity5. Density
    • Size andmorphology:Methods used are Photon correlation spectroscopy(PCS) Laser defractometry Transmission electron microscopy(TEM) Scanning electron microscopy(SEM) Atomic force microscopy Mercury porositometry Freeze fracture
    •  PCS and EM are widely used to determine the particle size. Better results are obtained using freeze fracture and photon correlation spectroscopy. Freeze fracture microscopy: In this poly (methyl methacrylate) is used. Only few particles are analyzed. This method also gives morphology of inner structure of particles.
    • CONTINUE…. Scanning electron microscopy: This measures individual particles. It is a less time taking process. Atomic force microcopy images can be obtained in an aqueous medium so this is an effective technique to investigate nanoparticle behavior in biological environment.
    • Scanning Electron Microscopy Field Emission SEM Transmission Electron Microscopy Atomic Force Microscopy
    • 2. Specific surface: the specific surface area of freeze dried nanoparticles is measured using sorptometer. The residual surfactant reduces the specific surface area.3. Surface charge and electrophoretic mobility: the nature and intensity of the surface charge of nanoparticles is very important as it determines their interaction with the biological environment. Surface charge measured using laser Doppler anemometry or velocimetry. Surface charge is also measured using electrophoretic mobility in phosphate saline buffer (7.4) and human serum.
    • 4. Surface hydrophobicity: the hydrophobicity determines the fate of nanoparticles and their contents. The measurement of angle of contact suggests about the hydrophilicity and hydrophobicity of the nanoparticles. Recently X-ray photoelectron spectroscopy is used to identify chemical groups on surface of nanoparticles.5. Density: the density of nanoparticles is determined with helium or air using a gas Pycnometer.
    • In vitro release profile of Drugs•Using standard dialysis or diffusion cell.•Double chamber diffusion cell on shaker stand.•The donor chamber is filled with nanoparticulatesuspension.•Receptor chamber with plain buffer.•The receptor chamber is assayed at different timeintervals using standard procedure.
    • In vivo fate and biodistribution of Nanoparticles RESnanoparticles Opsonin adsorption Phagocytosis recognition opsonins adsorb on to the surface of colloidal carriersand render particles recognizable to the “RES” thus theymediate their endocytosis by fixed macrophages of “RES”and circulating monocytes
    • Surface engineering of Nanoparticles Nanoparticles are surface engineered for various purposes.They are classified as Magnetically guided nanoparticles Bioadhesive guided nanoparticles Antibody guided nanoparticles
    • Magnetically guided NanoparticleMagnets can be used to deliver forces and energy, andcan be sensed remotelyMagnetic nanoparticles can be used both in vivo andin vitro, to great effectEndomagnetics has real promise for oncology,hematology, drug delivery, stem cell therapies
    • Nanoparticles are rendered magnetic by incorporating ironparticles (10-20nm) simultaneously with the drug during thepreparation stage; the magnetic nanoparticles are then injectedthrough the artery, supplying the tumour tissue and guidedexternally
    • Nanoparticles coated with Antibodies Target specific antibodies to the nanoparticle surfacemay facilitate their delivery to specific sites. Monoclonalantibodies can be fixed on nanoparticles by directadsorption or via a spacer molecule or by covalentlinkage, Tumour specific monoclonal antibodies conjugatedto super-paramagnetic monocrystalline iron oxidenanoparticles (MION) could be used to yield specificdiagnoses with the use of MR imaging
    • Nanoparticles for Bioadhesion Here the drug adhere to the mucosal surface and provide better opportunity for drug absorption in a controlled manner, the fate of nanoparticles follows three different pathways:1) Bioadhesion,2) translocation through the mucosa and3) transit and direct fecal elimination
    • APPLICATIONS Application PurposeCancer therapy Targeting and enhanced uptake of antitumor agentsIntracellular targeting Target intracellular infectionsProlonged systemic circulation To prolong the drug effectVaccine adjuvant Enhances immune responsePeroral absorption Enhanced bioavailabilityOcular delivery Improved retention of drug and reduced washoutOther applications Crosses blood-brain barrier Improved absorption Oral delivery of peptides.
    • Parenteral Administration Delivery of anticancer drugs Nanoparticles have been found to accumulate in tumors after IV administration Reduction in toxicity of anticancer drugs as drugs are concentrated mainly in liver and spleen Useful in treatment of hepatic metastases
    •  Material : poly (alkylcyanoacrylate) nanoparticles with steroids, anti-inflammatory agents, anti bacterial agents for glaucoma Purpose : improved retention of drug / reduced wash out. 74
    • Viral infections Nanoparticles represent an interesting for selective transport of antiviral agents displaying poor selectivity and/or short plasma half-life. For ex: nanoparticles loaded with protease inhibitor sesquinvir was shown to be effective in HIV infected human macrophage cultures
    •  Material : poly ( methylmethacrylate ) nanoparticles with vaccines ( oral and intramuscular immunization )  Purpose : enhances immune response, alternate acceptable adjuvant3/18/2013 56
    •  Material : Polyesters with adsorbed polyethylene glycols or pluronics or derivatized polyesters  Purpose : Prolong systemic drug effect, avoid uptake by the reticuloendothelial system3/18/2013 57
    • Various forms of nanoparticlesystems
    • COMMERCIAL PRODUCTS
    • Conclusion Polymeric particulate carrier systems are expected to target the inflamed tissue This new delivery system allows the desired drug toaccumulate In the inflamed tissue with high efficiency. The drug is concentrated at its site of action, whichreduces possible adverse effects and enhances the effectof the administered dose The sustained drug release allows pharmacological effectsto be extended due to the prolonged presence time of thecarrier system at the targeted inflamed area.
    • ReferencesVyas and Khar.Targeted and Controlled DrugDelivery Novel Carrier Systems.Firstedition,CBS Publishers, New Delhi.healthcare by sensing, moving and heatingmagnetic nanoparticles in the human body. QuentinPankhurst, Deputy Director: London Centre forNanotechnologyhttp://jpet.aspetjournals.org
    • REFERENCES Gilbert s Banker. Modern Pharmaceutics. 4 th edition. N.K. Jain. Controlled and Novel drug delivery. 1 st edition. Y.W. Chien. Novel Drug Delivery Systems. Binghe Wany, Teruna Siahaan, Richard A Soltao. Drug Delivery Principles and Applications. Krishna RSM, Shivakumar HG, Gowda DV and Benerjee S. Nanoparticles: A Novel colloidal drug delivery system. Ind J Pharm Ed Res.2006; 40(1):15-9.