Application microspheres

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By: rams349 (124 month(s) ago)

pls send dis ppt to [email protected]

By: naitik33 (124 month(s) ago)

i ll surely send u tht presentation ,, bt tell me .. who r u? whr r u from? wht r doin??

 

By: pavandyaga (125 month(s) ago)

hi man iam dong my m.pharm

By: pavurala (125 month(s) ago)

please send to my email

By: naitik33 (125 month(s) ago)

thx 4 d comment.. ll sure send u.. b4 tht.. tell me abt u smthng.. i mean studies., n al

 

By: pavandyaga (125 month(s) ago)

send me it on [email protected]

By: naitik33 (125 month(s) ago)

thx 4 d comment.. ll sure send u.. b4 tht.. tell me abt u smthng.. i mean studies., n al

 

By: pavandyaga (125 month(s) ago)

nice one but preparation is missing

By: naitik33 (125 month(s) ago)

seminar is only abt application so but obvious it doesnt contain preparation of microspheres..dnt mind

 
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Presentation Transcript

Slide 1:

Surface modified microspheres Microsponges Imaging Chemo immobilization Immuno microspheres Magnetic microspheres Targeting of drugs In vaccine delivery APPLICATIONS

MICROSPHERES IN VACCINE DELIVERY:

Ideal vaccine efficacy , safety , convenience in application cost . Safety, Prod of antibody responses Biodegradable delivery systems for vaccines that are given by PARENTERAL ROUTE may overcome the short coming of the conventional vaccine . MICROSPHERES IN VACCINE DELIVERY Improved antigenicity by adjuvant action, Modulation of antigen release, Stabilization of antigen. ADVANTAGES OF PARENTERAL CARRIER n mode of application.

Slide 3:

POLYMERS FOR VACCINE DELIVERY SYSTEM Biodegradable polymers choice for vaccinet do not require surgical removal. Different properties mode and rate of presentation of antigen, toxicity , tissue compatibility antigen stability polymer and method of preparation. Thermoplastic polyesters of poly(lactic acid), poly (glycolic acid) and co polymers PLGA

Slide 4:

Antigen Polymer used Method of preparation Reference Staphylococcus enterotoxin B di-PLGA Solvent evaporation Hora et al., 1990 Eldridge et a1., 1991 Diphtheria toxoid dl-PLA W/O/W emulsion Singh et a1., 1991 Hepatitis B surface antigen PGA Phase separation suspension Nellore et al., 1992 Tetanus toxoid PLA, PLGA Emulsion Esparza and Kissel 1992 Alonoso et al., 1992 Bovine serum alblumin PLA Adsorption Almeida et al., 1993 POLYMERS are studied extensively as the carrier for many antigens

Slide 5:

STABILITY Antigen-polymer compatibility barrier design of carrier stability problem Polymer compatibility By co-encapsulating buffer salts and stabilizers

Slide 6:

The use of tri block ABA copolymers having hydrophilic A block PLA or PLGA and hydrophilic B block also provide stability to the carrier system by providing more gentle and an accommodative system. Antigens are proteins that require specific three dimensional configurations for their activity.

Slide 7:

The factor which can alter the conformations are listed as Polymer Moisture Lyophilization pH Shearing Temperature Rotation Hydrophilic/Hydrophobic surface Salt Organic solvent

Slide 8:

The release of antigens from the microspheres is influenced by the structure , micro- morphology , nature and type of biodegradable polymer. The antigen release from microspheres can be of different types viz. Burst mechanism, Pore diffusion or combination of them. Erosion mechanism ANTIGEN RELEASE

Slide 9:

BURST MECHANISM Burst Mechanism Microsphere Antigen release

Slide 10:

PORE DIFFUSION Pore Diffusion Microsphere Antigen release

Slide 11:

EROSION MECHANISM

Microspheres and Immune System:

Microspheres and Immune System Interaction of microspheres with macrophages Microspheres with particle size less than 10 µm greater than 10 µm directly taken up by the antigen presenting cells degradation or release of antigens phagocytosized by antigen presenting cells

Slide 13:

The antigen presenting cells are responsible for the activation of B and T cells and hence immunological consequences A number of antigens are under investigation as shown on slide no.4 for their efficient delivery through microspheres.

MONOCLONAL ANTIBODIES MEDIATED MICROSPHERES TARGETING : IMMUNOMICROSPHERES::

The free Aldehyde groups, amino groups or hydroxyl group on the surface of microspheres can be linked to antibodies. The Mabs can be attached to the microspheres by any of the following methods; Non specific adsorption Specific adsorption Direct coupling via reagent MONOCLONAL ANTIBODIES MEDIATED MICROSPHERES TARGETING : IMMUNOMICROSPHERES: Monoclonal antibodies mediated targeting Selective targeting specific site (extremely specific) Mabs covalent coupling directly attached to microspheres

Magnetic Microspheres:

Magnetic Microspheres advantage of being efficient in allowing high local concentration of therapeutic agents magnetically responsive carriers Up to 60% of injected dose can be targeted and released to the selected non-endothelial organs In order to avoid toxicity due to focal overdosing a magnet with constant gradient may effectively be used. Magnetite containing matrices Ethyl- oleate based emulsion Natural cells such as erythrocyte ghosts

Slide 16:

mixing water soluble drugs (for lipophilic drugs, along with the dispersing agents) 10 nm magnetite (Fe 3 O 4 ) aqueous solvent of matrix material + + emulsified in the oil. Ultrasonication or shearing particle of suitable size range PREPARATION matrix is then stabilized by chemical Cross-linking or heating

Slide 17:

Magnetic microspheres in response to extra corporeal magnetic field get captured in small arterioles and capillaries of magnetic target organ. Magnetic microspheres Via intra-arterial intravenous administration OR high system targeting high pulmonary targeting or medium systemic targeting

Slide 18:

where, F = force on particles M = magnetic moment of particles VH = magnetic field gradients F = M VH Magnetic shielding is desirable to restrict the capture of the magnetic microspheres to the desired tissue and avoid adjacent tissue localization. Tissue carrier localization monitoring is also important in order to determine the free tissue level of drug at various times after targeting. Equation determining force can be given as :

Slide 19:

Solid tumours are first targeted using the adriamycin loaded magnetic microspheres. In rat tail model the tumour undergoes complete-remission in 75% of animal at a dose of 0.5 mg/kg. In a second study microspheres, targeted vindesin sulphate produce total remission of the tumours in 85% of rats at both 0.25 and 0.5 mg/kg dose levels. Amphotericin B is targeted for pulmonary aspergillosis using magnetic microspheres. Interleukin-2 is also targeted to stimulate the anti tumour response of the microphages using magnetic microspheres.

TARGETING USING MICRO PARTICULATE CARRIERS::

The concept of targeting, i.e. sites specific drug delivery is well established. The therapeutic efficacy of the drug relies on its access and specific interaction with its candidate receptors. The ability to leave the blood pool in reproducible, efficient and specific manner is center to drug action mediated by use of carrier system. Placement of the particles in discrete anatomical compartment leads to their retention either because of the physical property of the environment or biophysical interaction of the particle with cellular content of the target tissue. TARGETING USING MICRO PARTICULATE CARRIERS:

Slide 21:

The major objective of drug targeting must be to produce localized controlled release of broad spectrum agents within the extra vascular compartment of the desired organ or tissue. Efficient transport across micro vascular barrier can be achieved by: Magnetic dragging of the magnetic microparticle directly through endothelium and basement membrane. Facilitated transport of specific ligand drug conjugates (biochemical targeting) or coated microspheres ( bioadhesive targeting) across endothelium as a result of ligand binding to luminal surface antigen or receptor. Transient regional opening of endothelium function combined with vascular infusion of drug carrier that becomes sequestered in the extravascular complex.

CHEMOEMBOLIZATION:

Chemoembolization is an endovascular therapy which involve the selective arterial embolization of a tumor together with simultaneous or subsequent local delivery of chemotherapeutic agent. Chemoembolization is an extension of traditional percutaneous embolization techniques. Chemoembolization , investigators embolize tumor with micro particle soaked with chemotherapeutic agent. The theoretical advantage is that such embolization will not only provide vascular occlusive but will bring about sustained therapeutic levels of chemotherapeutics in the areas of tumor. Generalized ischemia so created would reduce the ability of the cell to relieve it self from the toxicity of chemotherapy. CHEMOEMBOLIZATION

Imaging:

Imaging The microspheres have been extensively used for the targeting purpose. various cells, cell lines, tissues and organs can be imaged using radio- labelled microspheres. The particle size range of microspheres is an important factor in determining the imaging of particular sites. The particles injected intravenously apart from the portal vein will become entrapped in the capillary bed of the lungs. This phemomenon is exploited for the scintiographic imaging of the tumour masses in lungs using labelled human serun albumin microspheres.

Micro sponges :Topical porous microspheres :

Micro sponges :Topical porous microspheres Micro sponges are porous microspheres having mydriad of interconnected voids of particles size range 5-300 µm. These micro sponges having capacity to entrap wide range of active ingredients such as emollients, fragrances, essential oils, sunscreens and anti- infectives , etc.

Slide 25:

The various steps in the preparation of micro sponge are summarized as: Selection of monomer or combination of monomers Formation of chain of monomers as polymerization begins Formation of ladders as a result of cross linking between chains of monomers Folding of monomer ladders to form spherical particles (microspheres) Agglomeration of microspheres, which gives rise to formation of bunches of microspheres Binding of bunches to form microsponges .

Slide 26:

The polymerization process leads to formation of reservoir type of system which opens at the surface through pores. In some cases the active substances are not capable of forming pores at the surface. In these cases an inert liquid immiscible with water but completely miscible with monomer is used during polymerization to form pore network. After polymerization the liquid is removed leaving the porous microspheres, i.e. microsponges . The functional substances are then incorporated by impregnating them within preformed microsponge . Sometimes solvent may be used for faster and efficient incorporation of the active substances. The micro- sponges act as the topical carriers for variety of functional substances, e.g. anti acne, anti inflammatory, anti pruritics anti fungal, rubefacients , etc.

Slide 27:

Surface Modified Microspheres The objective of drug therapy using carriers is the selective delivery of drug to specific sites in the body. The phagocytosis of colloidal carriers, rapid clearance and passive distribution are common disadvantages of particulate systems.

Slide 28:

Protein microspheres covalently modified by PEG derivatives show decreased immunogenecity and clearance. Among the most studied surface modifiers are Antibodies and their fragments. 2. Proteins. 3. Mono-, oligo -, and polysaccharides. 4.Chelating compounds (EDTA, DTPA or Desferroxamine ). 5. Synthetic soluble polymers.

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