Targeted drug delivery

1. A presentation by
SUBODH S SATHEESH
MPHARM, PHARMACEUTICS
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2. • It is a special form of drug delivery system where the
pharmacologically active agent or medicament is
selectively targeted or delivered only to its site of action
or absorption and not to the non-target organs or tissues
or cells.
• The drug may be delivered:
 To the capillary bed of the active sites.
 To the specific type of cell (or) even an intracellular
region. Ex- tumour cells but not to normal cells.
 To a specific organ (or) tissues by complexing with the
carrier that recognizes the target.
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3.  Pharmaceutical
• Drug instability in conventional dosage form
• Solubility
 Biopharmaceutical
• Low absorption
• High-membrane bounding
• Biological instability
 Pharmacokinetic / Pharmacodynamic
• Short half-life
• Large volume of distribution
• Low specificity
 Clinical
• Low therapeutic index.
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4. • Biochemically inert (non-toxic)
• Non-immunogenic.
• Both physically and chemically stable in vivo and in vitro.
• Should have uniform capillary distribution.
• Controllable and predicate rate of drug release.
• Drug release does not effect the drug action.
• Therapeutic amount of drug release
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5.  Physical
 Chemical
 biological
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6.  Soluble synthetic polymers
 Microspheres
 Nanoparticles
 Liposomes
 Polymeric micelles
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7.  substances that dissolve, disperse or swell in water
 modify the physical properties of aqueous systems in the
form of gellation, thickening or emulsification
 the polymer chains contain hydrophilic groups
 The hydrophilic groups may be nonionic, anionic, cationic
or amphoteric
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8. 3/19/2017 8DRUG TARGETING

9.  Poly dispersity index (PDI)
 PEG have low PDI
 Reactions catalyzed by anionic polymerization result in
PEGs with low PDI
 Enhances physical and chemical properties of drug
 PEG helps in reducing the aggregation of red blood cells
 PEG-drug conjugates have reduced protein
immunogenicity, increased residence time in the body,
reduced enzymatic degradation.
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10.  Polymerisation of vinyl acetate to
polyvinyl acetate
 PVA hydrogels have
pharmaceutical and biomedical
applications
 Nontoxic, noncarcinogenic,
nonadhesive
 PVA used for contact lenses, the
lining for artificial hearts, and
drug- delivery applications
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11.  PVP gives gives harder
granulates with good
flowability, higher binding and
low friability
 Enhances bioavailability
 good hydrophilization
properties, universal solubility
and ability to form water
soluble complexes
 PVP and polyvinyl pyrrolidone-
vinyl acetate (PVP-VA)
copolymer improves the
bioavailability of many poorly
water soluble drugs
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12.  a super adsorbent, in water
treatment
 it exists as a liquid at pH 5
and as a gel at pH 7
 Polyacrylic acid based
polymers are mainly used for
oral and mucosal contact
applications
 used as thickening,
suspending and emulsion
stabilizing agent in low
viscosity systems for topical
applications
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13. 3/19/2017 13DRUG TARGETING

14.  A di-block structure with a hydrophilic shell and a
hydrophobic core.
 The hydrophobic core generally consists of a
biodegradable polymer it act as a reservoir for an
insoluble drug.
 Non- or poorly biodegradable polymers can be used, as
long as they are not toxic to cells and can be renally
secreted
 Nature of the cell responsible for micellar stabilisation
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15.  Polymeric micelles are mostly small (10–100 nm) in size
and drugs can be incorporated by chemical conjugation or
physical entrapment
 PMs present a great potential for compounds that are
hydrophobic and exhibit poor bioavailability
 Block copolymers can be diblock copolymers or triblock
copolymers
 protection of the loaded drug from the harsh environment
of the GI tract
 release of the loaded drug in a controlled manner at target
sites
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16.  unfavorable interactions of the hydrophobic segments of
the lipid molecule with the solvent
 Liposomes consist of an aqueous core surrounded by a
lipid bilayer, much like a membrane, separating the inner
aqueous core from the bulk outside
 Lipos and soma
 Liposomes have been used to improve the therapeutic
index by modifying drug absorption
 Liposomal actions depend upon size, composition, loading
efficiency and stability, as well as their biological
interaction with the cell membranes.
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17.  Multi-lamellar vesicles(MLV)
Uni-lamellar vesicles
 Small unilamellar vesicles SUV
 Large unilamellar vesicles(LUV)
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18.  Passive loading techniques
 Active loading technique.
Passive loading techniques
 Mechanical dispersion method.
 Solvent dispersion method.
 Detergent removal method
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19.  Sonication.
 French pressure cell: extrusion.
 Freeze-thawed liposomes.
 Lipid film hydration by hand shaking, non-hand. shaking
or freeze drying.
 Micro-emulsification.
 Membrane extrusiogn.
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20.  Drying down lipids from organic solvent.
 Dispersing the lipid in aqueous media.
 Purifying the resultant liposome.
 Analyzing the final product.
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21. 3/19/2017 21DRUG TARGETING

22. Probe sonication
 The tip of a sonicator is directly
engrossed into the liposome
dispersion.
 The energy input into lipid
dispersion is very high in this
method.
 the vessel must be engrossed into a
water/ice bath.
 Throughout the sonication up to 1
h, more than 5% of the lipids can
be deesterified.
 the probe sonicator, titanium will
slough off and pollute the solution.
 The liposome dispersion in a
cylinder is placed into a bath
sonicator.
 Controlling the temperature of the
lipid dispersion is usually easy
 The material being sonicated can
be protected in a sterile vessel,
dissimilar the probe units, or under
an inert atmosphere .
Bath sonictaion
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23.  French pressure cell involves the extrusion of MLV
through a small orifice .
 The proteins do not seem to be significantly pretentious
during the procedure as they are in sonication .
 The method involves gentle handling of unstable
materials.
 The resulting liposomes are rather larger than sonicated
SUVs.
 high temperature is difficult to attain, and the working
volumes are comparatively small
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24. Ether injection
 A solution of lipids dissolved in
diethyl ether or ether-methanol
mixture
 It is gradually injected to an
aqueous solution of the material to
be encapsulated.
 The consequent removal of ether
under vacuum leads to the creation
of liposomes.
 The main disadvantages are that
the population is heterogeneous
(70 to 200 nm) and the exposure of
compounds high temperature.
 A lipid solution of ethanol is
rapidly injected to a huge excess of
buffer.
 The MLVs are formed.
 The disadvantages of the method
are that the population is
heterogeneous
 liposomes are very dilute, the
removal all ethanol is difficult
because it forms into azeotrope
with water.
Ethanol injection
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25. 3/19/2017 25DRUG TARGETING

26. dialysis
 The detergents at their critical
micelle concentrations (CMC)
have been used to solubilize lipids.
 the micelles become increasingly
better-off in phospholipid and
lastly combine to form LUVs.
 The dialysis can be performed in
dialysis bags engrossed in large
detergent free buffers
 detergent adsorbers eliminate
detergents with a very low CMC,
which are not entirely depleted.
 Aqueous mixed micellar solution
of detergent and phospholipids are
mixed with buffer
 micellar size and the
polydispersity increase
 system is diluted beyond the
mixed micellar phase boundary
 spontaneous transition from poly-
dispersed micelles to vesicles
occurs
dilution
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27.  completely biodegradable and nontoxic
 biologically inert and nonantigenic
 biocompatible and can be bioadhsive
 They can be used for delivering hydrophilic substances
 Encapsulated drug is protected from degradation
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28.  Liposomes above a certain size range can block capillaries
 The lipid components of liposomes may induce metabolic
changes and cause toxicity
 Sterility should be maintained in each step of production
and ingredients used should of highest purity
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29.  Treatment of cancer
 Intracellular parasitic diseases
 Metal toxicity
 Diabetes
 Cosmetics and dermatology
 Radiopharmaceutical carriers
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30.  Microspheres are small spherical particles, with diameters in
the micrometer range typically 1 μm to 1000 μm
 Glass microspheres, polymer microspheres and ceramic
microspheres
 Polyethylene and polystyrene microspheres
 Polystyrene microspheres are typically used in biomedical
application
 Polyethylene microspheres are commonly used as permanent or
temporary filler
 Microspheres vary widely in quality, sphericity, uniformity of
particle and particle size distribution
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31.  Spray drying
 Solvent evaporation
 Emulsion techniques
 Polymerisation techniques
 Solvent extraction
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32.  polymer is first dissolved in a suitable
solvent like dichloromethane, Acetone
 The drug in the solid form is then
dispersed in the polymer solution
under high-speed homogenization.
 This dispersion is then atomized in a
stream of hot air.
 The atomization leads to the formation
of the small droplets
 solvent evaporate instantaneously
leading the formation of the
microspheres in a size range 1-100μm.
 Micro particles are separated from the
hot air by means of the cyclone
separator
 trace of solvent is removed by vacuum
drying.
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33. 3/19/2017 33DRUG TARGETING

34.  microcapsule coating is dispersed in a volatile solvent
which is immiscible with the liquid manufacturing vehicle
phase
 A core material to be microencapsulated is dissolved or
dispersed in the coating polymer solution
 With agitation the core material mixture is dispersed in the
liquid manufacturing vehicle phase gives appropriate size
microcapsule
 core material is dissolved in the coating polymer solution,
matrix – type microcapsules are formed
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35. 3/19/2017 35DRUG TARGETING

36.  It involves removal of the organic phase by extraction of
the organic solvent.
 The method involves water miscible organic solvents
such as isopropanol.
 Organic phase is removed by extraction with water.
 It decreases the hardening time for then microspheres.
 direct addition of the drug or protein to polymer organic
solution.
 The rate of solvent removal by extraction method depends
on the temperature of water, ratio of emulsion volume to
the water and the solubility profile of the polymer.
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37.  Normal polymerisation
 Interfacial polymerisation
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38.  Bulk, suspension, precipitation, emulsion and micellar
polymerization Processes
 . In bulk, a monomer or a mixture of monomers along with the
initiator or catalyst is usually heated to initiate polymerization
 Suspension polymerisation is carried out by heating the
monomer or mixture of monomers as droplets dispersion in a
continuous aqueous phase.
 Emulsion polymerization differs from suspension
polymerization as due to the presence initiator in the aqueous
phase, which later on diffuses to the surface of micelles
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39.  It involves the reaction of various monomers at the interface
between the two immiscible liquid phases to form a film of
polymer that essentially envelops the dispersed phase
 This process is based on the principle of decreasing the
solubility of the polymer in organic phase to affect the
formation of polymer rich phase called the coacervates.
 The drug particles are dispersed in a solution of the polymer
and an incompatible polymer is added to the system which
makes first polymer to phase separate and engulf the drug
particles
 Poly lactic acid (PLA) microspheres have been prepared by
this method by using butadiene as incompatible polymer.
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40.  The micro particulate carriers of natural polymers of proteins and
carbohydrates are prepared by single emulsion technique.
 The natural polymers are dissolved or dispersed in aqueous medium
followed by dispersion in non-aqueous medium like oil.
 cross linking of the dispersed globule is carried out.
 The cross linking can be achieved either by means of heat or by using the
chemical cross linkers.
 The chemical cross linking agents used are glutaraldehyde, formaldehyde,
acid chloride etc.
 Chemical cross linking has disadvantage of excessive exposure of active
ingredient to chemicals.
 The nature of the surfactants used to stabilize the emulsion phases can
greatly influence the size, size distribution, surface morphology, loading,
drug release, and bio performance of the final multiparticulate product.

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41.  It involves the formation of the multiple emulsions or the
double emulsion of type w/o/w and is best suited to water
soluble drugs, peptides, proteins and the vaccines.
 The aqueous protein solution is dispersed in a lipophilic
organic continuous phase.
 The continuous phase is generally consisted of the polymer
solution that eventually encapsulates of the protein contained in
dispersed aqueous phase.
 The primary emulsion is subjected then to the homogenization
or the sonication
 The emulsion is then subjected to solvent removal either by
solvent evaporation or by solvent extraction
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42.  They are used in vaccine delivery
 Magnetic microspheres help in delivery of high
concentrations of therapeutic agents
 They are also used in imaging.
 Used as topical carriers of substances like antipyretic,
anti-inflammatory, antifungal etc
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43.  Ijpr carriers in drug targeting page 1-51
 Intechophenonline.com targeted drug delivery system1-34
 Hindawi.com polymeric micelles a promising drug
delivery system 1-16
 Researchgate.com targeted drug delivery systems page 27-
43
 Pubs.rsc.org drug targeting page 1-28
 S Bharath Pharmaceutical technology concepts and
applications 2013edition page 189-226.
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44. Thanks to all
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