This document discusses nanoparticles and their preparation techniques. Nanoparticles are subnanosized colloidal structures composed of synthetic or semi-synthetic polymers that can carry drugs or proteins. There are various methods to prepare nanoparticles, including cross-linking of amphiphilic macromolecules, polymerization methods, and polymer precipitation techniques. Nanoparticles find applications as drug delivery systems due to their ability to encapsulate and release drugs in a controlled manner.

1. NanoparticlesNanoparticles
Presented by:
Chinchole Pravin Sonu
(M.PHARM 2nd
SEM)
DEPARTMENT OF PHARMACEUTICS &
QUALITY ASSURANCE
R. C. Patel Institute of
Pharmaceutical Education and
Research, shirpur.

2. contentscontents
IntroductionIntroduction
Preparation techniques of nanoparticlesPreparation techniques of nanoparticles
Novel nanoparticulate systemsNovel nanoparticulate systems
Drug loading & in vitro release processDrug loading & in vitro release process
Pharmaceutical aspects of nanoparticlesPharmaceutical aspects of nanoparticles
Characterization of nanoparticlesCharacterization of nanoparticles
In vivo fate & biodistribution of nanoparticlesIn vivo fate & biodistribution of nanoparticles
Therapeutic applications of nanoparticlesTherapeutic applications of nanoparticles

3. Nanoparticles are subnanosized colloidal structures composed ofNanoparticles are subnanosized colloidal structures composed of
synthetic or semi synthetic polymerssynthetic or semi synthetic polymers
The polymeric nanoparticles can carry drugs or proteinacous substances,The polymeric nanoparticles can carry drugs or proteinacous substances,
antigens.antigens.
These bioactives are entrapped in the polymer matrix as particulatesThese bioactives are entrapped in the polymer matrix as particulates
enmesh or solid solution or may be bound to the particle surface byenmesh or solid solution or may be bound to the particle surface by
physical adsorption or chemicallyphysical adsorption or chemically
Nanospheres contain drug embedded within the matrix or adsorbed on toNanospheres contain drug embedded within the matrix or adsorbed on to
the surfacethe surface
Nanocapsules are vesicular system in which drug is essentiallyNanocapsules are vesicular system in which drug is essentially
encapsulated within central volume surrounded by an embryonicencapsulated within central volume surrounded by an embryonic
continuous polymeric sheathcontinuous polymeric sheath

4. Preparation tech. of nanoparticlesPreparation tech. of nanoparticles
(Polymers for nanoparticles)(Polymers for nanoparticles)
ProteinsProteins
GelatinGelatin
AlbuminAlbumin
LectinsLectins
LeguminLegumin
VicilinVicilin
polysaccharidespolysaccharides
AlginateAlginate
DextranDextran
ChitosanChitosan
AgaroseAgarose
PullulanPullulan

5. Various synthetic polymers used for prepration ofVarious synthetic polymers used for prepration of
nanoparticlesnanoparticles
PrepolymerisedPrepolymerised
Poly(e-caprolactone)Poly(e-caprolactone)
Polylactic acidPolylactic acid
Poly(lactide-co-glycolide)Poly(lactide-co-glycolide)
PolystyrenePolystyrene
Polymerised in processPolymerised in process
Poly(isobutylcynoacrylate)Poly(isobutylcynoacrylate)
Poly(butylcynoacrylate)Poly(butylcynoacrylate)
Poly(hexylcynoacrylate)Poly(hexylcynoacrylate)
PolymethylmethacrylatePolymethylmethacrylate

6. Selection of method for preparing nanoparticles depends onSelection of method for preparing nanoparticles depends on
the physicochemical characteristics of polymer & the drug tothe physicochemical characteristics of polymer & the drug to
be loaded. The preparation tech. determine the innerbe loaded. The preparation tech. determine the inner
structure, in vitro release profile & biological fate of thesestructure, in vitro release profile & biological fate of these
polymeric delivery system.polymeric delivery system.
The different systems includeThe different systems include
AA matrix typematrix type system consisting of ansystem consisting of an
entanglement of oligomer or polymer unitsentanglement of oligomer or polymer units
(nanoparticles /nanospheres)(nanoparticles /nanospheres)
AA reservoir typereservoir type of system consisting of an oilyof system consisting of an oily
core surrounded by an embryonic polymeric shellcore surrounded by an embryonic polymeric shell
(nanocapsules)(nanocapsules)
The drug can be entrapped or adsorbed on surfaceThe drug can be entrapped or adsorbed on surface
of these particulate systemof these particulate system

7. Method are classified asMethod are classified as
Amphiphilic macromolecule cross linkingAmphiphilic macromolecule cross linking
1.Heat crosslinking1.Heat crosslinking
2.Chemical crosslinking2.Chemical crosslinking
Polymerization based methodsPolymerization based methods
1. Polymerization of monomers in situ1. Polymerization of monomers in situ
2. Emulsion polymerization2. Emulsion polymerization
3. Dispersion polymerization3. Dispersion polymerization
4. Interfacial condensation polymerization4. Interfacial condensation polymerization
5. Interfacial complexation5. Interfacial complexation
Polymer precipitation methodsPolymer precipitation methods
Solvent extraction/evaporationSolvent extraction/evaporation
Solvent displacementSolvent displacement
Salting outSalting out

9. Polymers used for preparation of nanoparticles& nanocapsulesPolymers used for preparation of nanoparticles& nanocapsules
Polymer usePolymer use TechniqueTechnique Candidate drugCandidate drug
HydrophilicHydrophilic
Albumin, gelatinAlbumin, gelatin
Heat denaturation & crossHeat denaturation & cross
linking in w/o emulsionlinking in w/o emulsion
Desolvation &cross linking inDesolvation &cross linking in
aqueous mediumaqueous medium
HydrophilicHydrophilic
Hydrophilic & protein affinityHydrophilic & protein affinity
Alginate,chitosanAlginate,chitosan Cross linking in aq. mediumCross linking in aq. medium Hydrophilic & protein affinityHydrophilic & protein affinity
DextranDextran Polymer precipitation in anPolymer precipitation in an
organic solventorganic solvent
HydrophilicHydrophilic
HydrophobicHydrophobic
Poly(alkylcyanoacrylates)Poly(alkylcyanoacrylates)
Emulsion polymerizationEmulsion polymerization
Interfacial/polymerizationInterfacial/polymerization
HydrophilicHydrophilic
HydrophobicHydrophobic
PolyestersPolyesters
Poly(lactic acid,poly(lactide-co-Poly(lactic acid,poly(lactide-co-
glycolide)poly(glycolide)poly(€€-caprolactone-caprolactone))
Solvent extraction-evaporationSolvent extraction-evaporation
Solvent displacementSolvent displacement
Salting outSalting out
Hydrophilic ,HydrophobicHydrophilic ,Hydrophobic
Soluble in polar solventSoluble in polar solvent
Soluble in polar solventSoluble in polar solvent

10. Method of preparation for nanoparticlesMethod of preparation for nanoparticles
Amphillic macromolecules that undergo a crosslinkingAmphillic macromolecules that undergo a crosslinking
reaction during preparation of nanospheresreaction during preparation of nanospheres
Monomers that polymerize during formation of nanospheresMonomers that polymerize during formation of nanospheres
Hydrophobic polymers which are initially dissolved in organicHydrophobic polymers which are initially dissolved in organic
solvents & then precipitated under controlled conditions tosolvents & then precipitated under controlled conditions to
produce nanospheresproduce nanospheres

11. Nanoparticles preparation by cross linking of amphiphilicNanoparticles preparation by cross linking of amphiphilic
macromoleculesmacromolecules
It can be prepared from amphiphilic macromolecules, proteins &It can be prepared from amphiphilic macromolecules, proteins &
polysaccharides which have affinity for aq.&lipid solvents.polysaccharides which have affinity for aq.&lipid solvents.
The tech.of their preparation involves the aggregation of amphiphiles followedThe tech.of their preparation involves the aggregation of amphiphiles followed
by further stabilization either by heat denaturation or chemical cross linking.by further stabilization either by heat denaturation or chemical cross linking.
Cross linking in w/o emulsionCross linking in w/o emulsion
1. The method involves the emulsification of bovine serum albumin/human1. The method involves the emulsification of bovine serum albumin/human
serum albumin or protein aq. solution in oil using high pressureserum albumin or protein aq. solution in oil using high pressure
homogenization or high frequency sonicationhomogenization or high frequency sonication
2. The w/o emulsion so formed is poured into preheated oil. The suspension in2. The w/o emulsion so formed is poured into preheated oil. The suspension in
preheated oil maintained above 100preheated oil maintained above 10000
C is held stirred for time in order toC is held stirred for time in order to
denature & aggregate the protein contents of aq. pool completely & todenature & aggregate the protein contents of aq. pool completely & to
evaporate waterevaporate water
3. The particles are finally washed with organic solvent to remove any oil traces3. The particles are finally washed with organic solvent to remove any oil traces
& collected by centrifugation& collected by centrifugation
4. The main factors are emulsification energy & temperature (used for4. The main factors are emulsification energy & temperature (used for
denaturation & aggregationdenaturation & aggregation

13. Phase separation in aqueous medium (desolvation)Phase separation in aqueous medium (desolvation)
The protein or polysaccharide from an aq. phase can be desolvated byThe protein or polysaccharide from an aq. phase can be desolvated by
PH change or temp change or by adding counter ions. Cross linking mayPH change or temp change or by adding counter ions. Cross linking may
be affected simultaneously or next to the desolvation stepbe affected simultaneously or next to the desolvation step
Steps are protein dissolution, protein aggregation & proteinSteps are protein dissolution, protein aggregation & protein
deaggregationdeaggregation
Solvent competing agent ,sodium sulphate is mainly used as aSolvent competing agent ,sodium sulphate is mainly used as a
desolvating agent while alcohol are added as desolvating ordesolvating agent while alcohol are added as desolvating or
deaggregating agentdeaggregating agent
Addition can be optimized turbid metrically using Nephelometer.Addition can be optimized turbid metrically using Nephelometer.

14. Aqueous phase (Protein
aq.solution)
Protein aggregates (coacervates)
Desolvation (solvent
competing agent)
Protein colloidal dispersion
Nanoparticle suspension (external aq.
Phase)
Crosslinking
(aldehyde)
Resolvation
(alcohol)
Nanoparticle preparation by desolvation in an aq. medium technique

16. PPHH
induced aggregationinduced aggregation
Gelatin & Tween 20 were dissolved in aq. phase & PGelatin & Tween 20 were dissolved in aq. phase & PHH
was adjusted towas adjusted to
optimum value. Solutions were heated ,then quenching at 4oC for 24h.Theoptimum value. Solutions were heated ,then quenching at 4oC for 24h.The
leads to colloidal dispersion of aggregated gelatin. The aggregates wereleads to colloidal dispersion of aggregated gelatin. The aggregates were
finally cross linked using glutaraldehyde.The size of nanospheres were offinally cross linked using glutaraldehyde.The size of nanospheres were of
200 nm. The ideal P200 nm. The ideal PHH
range is 5.5-6.5.range is 5.5-6.5.
Counter ion induced aggregationCounter ion induced aggregation
Separation of protein phase may occur by the presence of counter ions inSeparation of protein phase may occur by the presence of counter ions in
the aqueous medium.the aqueous medium.
The aggregation can be propagated by adding counters ions followed byThe aggregation can be propagated by adding counters ions followed by
rigidization step.rigidization step.
Chitosan nanospheres can be prepared by addingChitosan nanospheres can be prepared by adding tripolyphosphatetripolyphosphate to theto the
medium.medium.
Alginate nanoparticles can be prepared by gelation withAlginate nanoparticles can be prepared by gelation with calcium ionscalcium ions

17. Nanoparticles prepared by polymerization methodsNanoparticles prepared by polymerization methods
The polymers used for nanospheres preparation include polyThe polymers used for nanospheres preparation include poly
(methylmethacrylate) poly(acrylamide)poly(butyl cyanoacrylate).(methylmethacrylate) poly(acrylamide)poly(butyl cyanoacrylate).
The different methods using in situ polymerization tech. areThe different methods using in situ polymerization tech. are
Methods in which the monomer to be polymerised is emulsified in a nonMethods in which the monomer to be polymerised is emulsified in a non
solvent phase orsolvent phase or (emulsion polymerization)(emulsion polymerization)
Methods in which the monomer is dissolved in a solvent that is nonMethods in which the monomer is dissolved in a solvent that is non
solvent for the resulting polymersolvent for the resulting polymer (Dispersion polymerization)(Dispersion polymerization)
In EP method the monomer is dissolved in an internal phase while inIn EP method the monomer is dissolved in an internal phase while in
case of DP it is taken in dispersed phasecase of DP it is taken in dispersed phase
In both cases after polymerization polymer tends to be insoluble inIn both cases after polymerization polymer tends to be insoluble in
internal phase & results into suspension of nanospheresinternal phase & results into suspension of nanospheres

18. Emulsion polymerizationEmulsion polymerization
Micellar polymerizationMicellar polymerization
The mechanism involved are micellar nucleation & polymerization &The mechanism involved are micellar nucleation & polymerization &
homogenous nucleation & polymerizationhomogenous nucleation & polymerization
The first includes swollen monomer micelles as the site of nucleation &The first includes swollen monomer micelles as the site of nucleation &
polymerization.polymerization.
The monomer is emulsified in the non solvent phase with the help ofThe monomer is emulsified in the non solvent phase with the help of
surfactant molecules.surfactant molecules.
The process leads to formation of monomer swollen micelles which hasThe process leads to formation of monomer swollen micelles which has
size in nanometric range.size in nanometric range.
The polymerization reaction proceeds through nucleation & propogationThe polymerization reaction proceeds through nucleation & propogation
in the presence of chemical or physical initiatorin the presence of chemical or physical initiator

20. Homogeneous polymerizationHomogeneous polymerization
Monomer is sufficiently soluble in the continuous outer phaseMonomer is sufficiently soluble in the continuous outer phase
Formation of primary chains (oligomers)Formation of primary chains (oligomers)
At certain length oligomers precipitate & forms primary particlesAt certain length oligomers precipitate & forms primary particles
which are stabilized by surfactantwhich are stabilized by surfactant
Addition of monomer input or fusion of primary particles formsAddition of monomer input or fusion of primary particles forms
nanoparticlesnanoparticles

22. Water soluble drugs may be associated with PACAWater soluble drugs may be associated with PACA
nanoparticles either by dissolving the drug in thenanoparticles either by dissolving the drug in the
aqueous polymerization medium or by incubating theaqueous polymerization medium or by incubating the
blank nanospheres with an aq. solution of drugblank nanospheres with an aq. solution of drug
Drug molecules may be entrapped within the polymerDrug molecules may be entrapped within the polymer
matrix & are also adsorbed onto the surface ofmatrix & are also adsorbed onto the surface of
nanoparticlesnanoparticles
Drug molecules may be physically adsorbed on theDrug molecules may be physically adsorbed on the
surfacesurface

24. Dispersion polymerizationDispersion polymerization
In emulsion polymerization monomer is emulsified in anIn emulsion polymerization monomer is emulsified in an
immiscible phase using surfactant.In case of dispersionimmiscible phase using surfactant.In case of dispersion
polymerization monomer is dissolved in an aqueouspolymerization monomer is dissolved in an aqueous
medium which acts as precipitant for polymermedium which acts as precipitant for polymer
The monomer is introduced into the dispersion medium.The monomer is introduced into the dispersion medium.
Polymerization is initiated by adding a catalyst &Polymerization is initiated by adding a catalyst &
proceeds with nucleation phase followed by growthproceeds with nucleation phase followed by growth
phase.phase.

25. Inverse emulsification polymerization mechanismInverse emulsification polymerization mechanism

26. Emulsion polymerization processEmulsion polymerization process

28. The nucleation is directly induced in the aqueousThe nucleation is directly induced in the aqueous
monomer solution &monomer solution & the presence of stabilizer orthe presence of stabilizer or
surfactant is not requiredsurfactant is not required
The acrylamide or methyl methacrylate monomer isThe acrylamide or methyl methacrylate monomer is
dissolved in aqueous phase & polymerized by gammadissolved in aqueous phase & polymerized by gamma
irradiationirradiation
By chemical initiation (ammonium or potassiumBy chemical initiation (ammonium or potassium
peroxodisulphate) combined with heating to temp. aboveperoxodisulphate) combined with heating to temp. above
6565 00
CC
PMMA nanoparticles can be prepared by gammaPMMA nanoparticles can be prepared by gamma
irradiation in the presence of antigenic materialirradiation in the presence of antigenic material
e.g. influenza virion, influenza sub unit antigen, bovinee.g. influenza virion, influenza sub unit antigen, bovine
serum albumin, HIV-1 & HIV-2 antigensserum albumin, HIV-1 & HIV-2 antigens

29. Interfacial polymerizationInterfacial polymerization
The preformed polymer phase is finally transformed to anThe preformed polymer phase is finally transformed to an
embryonic sheath.embryonic sheath.
The polymer & drug are dissolved in a volatile solvent. TheThe polymer & drug are dissolved in a volatile solvent. The
solution is is poured into a non solvent for both polymer & coresolution is is poured into a non solvent for both polymer & core
phase.phase.
The polymer phase is separated as as a coacervate phase at o/wThe polymer phase is separated as as a coacervate phase at o/w
interface. The mixture turns milky due to formation ofinterface. The mixture turns milky due to formation of
nanocapsules.nanocapsules.
This method is used for proteins, enzymes, antibodies, & cellsThis method is used for proteins, enzymes, antibodies, & cells
Interfacial polymeric condensation of 2,2-bis-(4hydroxyphenyl)Interfacial polymeric condensation of 2,2-bis-(4hydroxyphenyl)
propane & sebacoyl chloridepropane & sebacoyl chloride
The size of nanocapsules ranges from 30-300nmThe size of nanocapsules ranges from 30-300nm

31. Nanoparticle preparation using emulsion solventNanoparticle preparation using emulsion solvent
evaporation methodevaporation method

32. Hydrophobic polymer & or hydrophobic drug is dissolved in a organicHydrophobic polymer & or hydrophobic drug is dissolved in a organic
solvent followed by its dispersion in a continuous aq. Phase in which thesolvent followed by its dispersion in a continuous aq. Phase in which the
polymer is insoluble. External phase contains stabilizer.polymer is insoluble. External phase contains stabilizer.
Depending upon solvent miscibility tech.may called as solvent extractionDepending upon solvent miscibility tech.may called as solvent extraction
or evaporation methodor evaporation method
The polymer precipitation is done byThe polymer precipitation is done by
Increasing the solubility of organic solvent in the external medium byIncreasing the solubility of organic solvent in the external medium by
adding an alcohol (isopropanol)adding an alcohol (isopropanol)
By incorporating water into ultraemulsion(to extract solvent)By incorporating water into ultraemulsion(to extract solvent)
By evaporation of solvent at room temp. by using vacuumBy evaporation of solvent at room temp. by using vacuum
Using an organic solvent which is completely soluble in the continuousUsing an organic solvent which is completely soluble in the continuous
aq.phase(acetone)nanoprecipitationaq.phase(acetone)nanoprecipitation

33. Solvent extraction methodSolvent extraction method
This method involves the preparation of o/w emulsionThis method involves the preparation of o/w emulsion
The subsequent removal of solvent or the addition of water to theThe subsequent removal of solvent or the addition of water to the
system so as to affect diffusion of solvent to external phasesystem so as to affect diffusion of solvent to external phase
(emulsification diffusion method)(emulsification diffusion method)
The solvent used for polymer is poorly miscible with dispersion phase &The solvent used for polymer is poorly miscible with dispersion phase &
thus diffuses & evaporates out slowly on continual stirringthus diffuses & evaporates out slowly on continual stirring
Dispersion medium miscible polymer solvent (alcohol & acetoneDispersion medium miscible polymer solvent (alcohol & acetone
instantaneously diffuses into the aq. phase & polymer precipitates asinstantaneously diffuses into the aq. phase & polymer precipitates as
tiny nanospherestiny nanospheres

35. Solvent displacement methodSolvent displacement method
It is based on interfacial deposition of a polymer followingIt is based on interfacial deposition of a polymer following
displacement of a semi polar solvent miscible with waterdisplacement of a semi polar solvent miscible with water
from a lipophilic solutionfrom a lipophilic solution
The organic solvent diffuses instantaneously to the externalThe organic solvent diffuses instantaneously to the external
aq. Phase inducing immediate polymer precipitation becauseaq. Phase inducing immediate polymer precipitation because
of complete miscibility of both the phasesof complete miscibility of both the phases
If drug is highly hydrophilic it diffuses out into the external aq.If drug is highly hydrophilic it diffuses out into the external aq.
phase while if drug is hydrophobic it precipitates in aq.phase while if drug is hydrophobic it precipitates in aq.
medium as nanocrystalsmedium as nanocrystals

36. Solvent displacement methodSolvent displacement method

37. Salting outSalting out

38. The method involves the incorporation of a saturated aq. solution ofThe method involves the incorporation of a saturated aq. solution of
polyvinyl alcohol into an acetone solution of polymer under magneticpolyvinyl alcohol into an acetone solution of polymer under magnetic
stirring to form an o/w emulsion.stirring to form an o/w emulsion.
In nanoprecipitationIn nanoprecipitation tech.polymeric solution istech.polymeric solution is completely misciblecompletely miscible
with external aq. mediumwith external aq. medium.. But in this methodBut in this method miscibility of both themiscibility of both the
phases is prevented byphases is prevented by saturation of external aq .phase with PVA.saturation of external aq .phase with PVA.
Precipitation of polymer occurs when sufficient amount of water isPrecipitation of polymer occurs when sufficient amount of water is
added to external phase to allow complete diffusion of acetone fromadded to external phase to allow complete diffusion of acetone from
internal phase to aq.phaseinternal phase to aq.phase
This method is suitable for drugs & polymers that are soluble in polarThis method is suitable for drugs & polymers that are soluble in polar
solvents such as acetone & ethanolsolvents such as acetone & ethanol

39. Solid lipid nanoparticlesSolid lipid nanoparticles
The solid lipid nanoparticles are submicron colloidalThe solid lipid nanoparticles are submicron colloidal
carriers which are composed of physiological lipidcarriers which are composed of physiological lipid
,dispersed in water or in an aqueous surfactant solution,dispersed in water or in an aqueous surfactant solution
It combines the advantages of polymeric nanoparticles,It combines the advantages of polymeric nanoparticles,
fat emulsions & liposomesfat emulsions & liposomes
The liquid lipid was replaced by a solid lipid whichThe liquid lipid was replaced by a solid lipid which
transformed into solid lipid nanoparticlestransformed into solid lipid nanoparticles

40. AdvantagesAdvantages
Small size & narrow size distribution provides for site specific drugSmall size & narrow size distribution provides for site specific drug
delivery by SLNsdelivery by SLNs
Controlled release of active drug over a long period can be achievedControlled release of active drug over a long period can be achieved
Protection of incorporated drug against chemical degradationProtection of incorporated drug against chemical degradation
SLNs can be lyophilized & spray driedSLNs can be lyophilized & spray dried
No toxic metabolites are producedNo toxic metabolites are produced
Sterilization can be done by autoclaving or gamma irradiationSterilization can be done by autoclaving or gamma irradiation
Surface modification can be easily doneSurface modification can be easily done

41. Preparation of SLNPreparation of SLN
Melting of the lipid
Dissolution of drug in melted lipid
Mixing of preheated dispersion medium & drug lipid melt
Premix using stirrer to form coarse pre-emulsion
High pressure homogenization at a temp. above the lipids melting point
o/w nanoemulsion
Solidification of the nanoemulsion by cooling down to room temp. to form SLN
Hot Homogenization Technique

42. Preparation of SLNPreparation of SLN
Melting of the lipid
Dissolution /solubilization of drug in melted lipid
Solidification of drug loaded lipid in liquid nitrogen or dry ice
Grinding in a powder mill(50-100µm particles)
Dispersion of lipid in the cold aqueous dispersion medium
Solid lipid nanoparticles
Cold Homogenization Technique

43. Nanocrystals and nanosuspensionNanocrystals and nanosuspension

44. Pharmaceutical aspects of nanoparticlesPharmaceutical aspects of nanoparticles
The important process parameters performed are Purification, FreezeThe important process parameters performed are Purification, Freeze
drying, Sterilizationdrying, Sterilization
Purification of nanoparticlesPurification of nanoparticles:-Toxic impurities includes organic:-Toxic impurities includes organic
solvents, residual monomers, polymerization initiators, electrolytes,solvents, residual monomers, polymerization initiators, electrolytes,
stabilizers & large polymer aggregates. Most commonly used method isstabilizers & large polymer aggregates. Most commonly used method is
gel filtration & ultra filtrationgel filtration & ultra filtration
Freeze drying of nanoparticlesFreeze drying of nanoparticles
It includes freezing of nanoparticle suspension & sublimation of water toIt includes freezing of nanoparticle suspension & sublimation of water to
produce free flowing powder.produce free flowing powder.
Advantages areAdvantages are
Prevention from degradation & or solubilization of the polymerPrevention from degradation & or solubilization of the polymer
Prevention from drug leakage, drug desorption, drug degradationPrevention from drug leakage, drug desorption, drug degradation
Nanocapsules containing oily core may be processed in the presence ofNanocapsules containing oily core may be processed in the presence of
mono or disaccharides (glucose or sucrose)mono or disaccharides (glucose or sucrose)
Readily dispersible in water without modifications in theirReadily dispersible in water without modifications in their
physicochemical propertiesphysicochemical properties

45. Sterilization of NanoparticlesSterilization of Nanoparticles
Nanoparticles for parenteral use should be sterilized to be pyrogen freeNanoparticles for parenteral use should be sterilized to be pyrogen free
before animal or human use.before animal or human use.
Sterilization in nanoparticles is achieved by using asepticSterilization in nanoparticles is achieved by using aseptic
tech.throughout their preparation & processing & formulation & bytech.throughout their preparation & processing & formulation & by
sterilizing treatments like autoclaving orsterilizing treatments like autoclaving or γγ-- irradiationirradiation

46. Characterization of nanoparticlesCharacterization of nanoparticles
ParameterParameter Characterization methodCharacterization method
Particle size & size distributionParticle size & size distribution Photon correlation spectroscopy,LaserPhoton correlation spectroscopy,Laser
defractometry,Transmission electrondefractometry,Transmission electron
microscopy,SEM,Atomic forcemicroscopy,SEM,Atomic force
microscopy,Mercury porosimetrymicroscopy,Mercury porosimetry
Charge determinationCharge determination Laser doppler anemometry, ZetaLaser doppler anemometry, Zeta
potentiometerpotentiometer
Surface hydrophobicitySurface hydrophobicity Water contact angle measurements, roseWater contact angle measurements, rose
bengal binding X-ray photoelectronbengal binding X-ray photoelectron
spectroscopyspectroscopy
Chemical analysis of surfaceChemical analysis of surface Static secondary ion mass spectrometry,Static secondary ion mass spectrometry,
sorptometersorptometer
Carrier-drug interactionCarrier-drug interaction Differential scanning calorimetryDifferential scanning calorimetry
Nanoparticle dispersion stabilityNanoparticle dispersion stability Critical flocculation temp (CFT)Critical flocculation temp (CFT)
Release profileRelease profile In vitro release charac.under physiologic &In vitro release charac.under physiologic &
sink conditionssink conditions
Drug stabilityDrug stability Bioassay of drug extracted fromBioassay of drug extracted from
nanoparticlesnanoparticles
Chemical analysis of drugChemical analysis of drug

47. Size & morphologySize & morphology
EM(SEM & TEM) are widely used for determining particle size & itsEM(SEM & TEM) are widely used for determining particle size & its
distribution.distribution.
Freeze fracturing of particles allows for morphological determination ofFreeze fracturing of particles allows for morphological determination of
inner structure of particles.inner structure of particles.
TEM permits differentiation among nanocapsules, nanoparticles, &TEM permits differentiation among nanocapsules, nanoparticles, &
emulsion dropletsemulsion droplets
Atomic force microscopy (AFM) images can be obtained in an aq.mediumAtomic force microscopy (AFM) images can be obtained in an aq.medium
hence used for investigation of nanoparticle behavior in biologicalhence used for investigation of nanoparticle behavior in biological
environment.environment.
Specific surfaceSpecific surface:-Is determined with the help of Sorptometer:-Is determined with the help of Sorptometer
Surface charge & electrophoretic mobility:-The nature & intensity ofSurface charge & electrophoretic mobility:-The nature & intensity of
surface charge determines their interaction with biological environment assurface charge determines their interaction with biological environment as
well as with bioactive compounds.It is determined by measuring thewell as with bioactive compounds.It is determined by measuring the
particle velocity in an electric field. (Laser doppler anemometry)particle velocity in an electric field. (Laser doppler anemometry)
The surface charge of colloidal particles is measured as electrophoreticThe surface charge of colloidal particles is measured as electrophoretic
mobility which is determined in phosphate saline buffer & human serummobility which is determined in phosphate saline buffer & human serum

48. Surface hydrophobicitySurface hydrophobicity:-influences in interaction with biological:-influences in interaction with biological
environmentenvironment
( Protein particles & cell adhesion). It is determined by two phase( Protein particles & cell adhesion). It is determined by two phase
partition,contact angle measurements, adsorption of hydrophobicpartition,contact angle measurements, adsorption of hydrophobic
fluorescent or radiolabelled probes.fluorescent or radiolabelled probes.
X-ray photoelectron spectroscopy permits the identification of specificX-ray photoelectron spectroscopy permits the identification of specific
chemical groups on the surface o nanoparticles.chemical groups on the surface o nanoparticles.
DensityDensity:-The density of nanoparticles is determined with helium or:-The density of nanoparticles is determined with helium or
air using a gas Pycnometerair using a gas Pycnometer
Molecular weight measurement of nanoparticlesMolecular weight measurement of nanoparticles:-:- Molecular weight ofMolecular weight of
the polymer & its distribution in the matrix can be evaluated by gelthe polymer & its distribution in the matrix can be evaluated by gel
permeation chromatography using a refractive index detector.permeation chromatography using a refractive index detector.
Nanoparticle recovery & drug incorporation efficiency:-Nanoparticle recovery & drug incorporation efficiency:-NanoparticleNanoparticle
yield can be calculated asyield can be calculated as
nanoparticles recovery(%)=nanoparticles recovery(%)= Conc. of drug in nanoparticlesConc. of drug in nanoparticles *100*100
conc of nanoparticles recoveredconc of nanoparticles recovered

49. Drug incorporation efficiency or drug contentDrug incorporation efficiency or drug content:-:-
Drug content(% w/w) =Drug content(% w/w) = Conc of drug in nanoparticles *100Conc of drug in nanoparticles *100
conc of nanoparticles recoveredconc of nanoparticles recovered
In vitro releaseIn vitro release:-:-In vitro release profile can be determined using standardIn vitro release profile can be determined using standard
dialysis, diffusion cell or modified ultrafiltration techniquedialysis, diffusion cell or modified ultrafiltration technique

50. In vivo fate & biodistribution of nanoparticlesIn vivo fate & biodistribution of nanoparticles
The plasma proteins (opsonins) adsorb on to the surface of colloidalThe plasma proteins (opsonins) adsorb on to the surface of colloidal
carriers & render particles recognizable to RES.carriers & render particles recognizable to RES.
Phagocytosis of particulates by elements of RES( liver, spleen,Phagocytosis of particulates by elements of RES( liver, spleen,
bone marrow), liver( Kupffer cells )is regulated by opsonins &bone marrow), liver( Kupffer cells )is regulated by opsonins &
disopsonins (IgA)disopsonins (IgA)

51. Surface engineering of nanoparticlesSurface engineering of nanoparticles
Steric stabilized (stealth) nanoparticlesSteric stabilized (stealth) nanoparticles
Bio-mimetic nanoparticlesBio-mimetic nanoparticles
Antibody coated nanoparticlesAntibody coated nanoparticles
Magnetically guided nanoparticlesMagnetically guided nanoparticles
Bioadhesive nanoparticlesBioadhesive nanoparticles
Steric stabilized (stealth) nanoparticles:-Steric stabilized (stealth) nanoparticles:-PEO is most commonly usedPEO is most commonly used
synthetic material to modify interactions of particles with serumsynthetic material to modify interactions of particles with serum
components. amphiphilic copolymers rather than homopolymer havecomponents. amphiphilic copolymers rather than homopolymer have
been shown to be effective in steric stabilization. Polysorbates 20,40,60 &been shown to be effective in steric stabilization. Polysorbates 20,40,60 &
80 & poloxamers are used for surface modification of PMMA80 & poloxamers are used for surface modification of PMMA
nanoparticlesnanoparticles

52. Bioadhesive nanoparticles:-covalent coupling of different ligands,Bioadhesive nanoparticles:-covalent coupling of different ligands, tomatotomato
lectin, asparagus pea lectinlectin, asparagus pea lectin
Bio-mimetic nanoparticles:-Bio-mimetic nanoparticles:- albuminalbumin which is main protein has beenwhich is main protein has been
reported as biomimitic ligand.reported as biomimitic ligand. Sialic acidSialic acid also serves the samealso serves the same
Magnetically guided nanoparticles:-Nanoparticles are rendered magneticMagnetically guided nanoparticles:-Nanoparticles are rendered magnetic
by incorporatingby incorporating FeFe33OO44 particles(10-20 nm)particles(10-20 nm) with drug during preparationwith drug during preparation
stage. Particles are injected through artery of tumour tissue & guidedstage. Particles are injected through artery of tumour tissue & guided
externally by external magnetic fieldexternally by external magnetic field
Iron oxide nanoparticles are also reportedIron oxide nanoparticles are also reported
Antibody coated nanoparticles:- Selectivity in drug targeting can beAntibody coated nanoparticles:- Selectivity in drug targeting can be
achieved by attachingachieved by attaching monoclonal antibodymonoclonal antibody as a site directing device.as a site directing device.
Mab can be fixed by direct adsorption or via aMab can be fixed by direct adsorption or via a spacer moleculespacer molecule or byor by
covalent linkagecovalent linkage using carbodiimide, glutaraldehyde reaction.using carbodiimide, glutaraldehyde reaction.

53. Therapeutic applications of nanoparticlesTherapeutic applications of nanoparticles
Biodegradable polymers like gelatin, albumin, casein,Biodegradable polymers like gelatin, albumin, casein,
polysaccharide,lectin & synthetic polymers like polycaprolactone,polysaccharide,lectin & synthetic polymers like polycaprolactone,
polyesters, polyanhydrides, polycyanoacrylates with various drugpolyesters, polyanhydrides, polycyanoacrylates with various drug
release charac. have been used to formulate sustained releaserelease charac. have been used to formulate sustained release
nanoparticles.nanoparticles.
Intracellular targeting:-Intracellular targeting:-available antibiotics has followingavailable antibiotics has following
limitationslimitations
Poor intracellular diffusionPoor intracellular diffusion
Most intracellular infections are difficult to irradicate becauseMost intracellular infections are difficult to irradicate because
bacteria inside phagosome are protected from antibioticsbacteria inside phagosome are protected from antibiotics
The need for antibiotics with greater intracellular efficacy led to theThe need for antibiotics with greater intracellular efficacy led to the
development of endocytosable drug carriers including nanoparticlesdevelopment of endocytosable drug carriers including nanoparticles

54. Various intracellular bacterial & parasitic infections whereVarious intracellular bacterial & parasitic infections where
Nanoparticle loaded antibiotics are usedNanoparticle loaded antibiotics are used
LeshmaniasisLeshmaniasis
SalmonellosisSalmonellosis
TrypanosisTrypanosis
MalariaMalaria
Prolonged systemic circulationProlonged systemic circulation can be achieved by surfacecan be achieved by surface
modification of nanoparticles withmodification of nanoparticles with different block polymersdifferent block polymers
(pluronics) or polyethylene glycols(pluronics) or polyethylene glycols

55. Nanoparticles in chemotherapyNanoparticles in chemotherapy
Antitumour agents that are either entrapped or adsorbed ontoAntitumour agents that are either entrapped or adsorbed onto
polyalkylcyanoacrylate nanoparticles(doxorubicin)polyalkylcyanoacrylate nanoparticles(doxorubicin)
Chemoembolizatiuon makes use of biodegradable particlesChemoembolizatiuon makes use of biodegradable particles
administration to the liver tumours using a cathetor that passes directlyadministration to the liver tumours using a cathetor that passes directly
into an artery of the tumorsinto an artery of the tumors
Enhanced endocytic activity & leaky vasculature of the tumour favoursEnhanced endocytic activity & leaky vasculature of the tumour favours
accumulation of intravenously administered nanoparticlesaccumulation of intravenously administered nanoparticles

56. ChemoembolizationChemoembolization

57. Adjuvant effect for vaccinesAdjuvant effect for vaccines
On SC injection sustained release of the entrapped antigen inducedOn SC injection sustained release of the entrapped antigen induced
significant antibody response & protected mice against a challenge withsignificant antibody response & protected mice against a challenge with
mouse adapted influenza virus to a greater extentmouse adapted influenza virus to a greater extent
A decrease in particle size & an increase in hydrophobicity of theA decrease in particle size & an increase in hydrophobicity of the
nanoparticles increased the adjuvant effect.nanoparticles increased the adjuvant effect.
Nanoparticles for peroral administration of proteins & peptides:-Nanoparticles for peroral administration of proteins & peptides:-asas
they are susceptible to proteolytic degradation, hence leades tothey are susceptible to proteolytic degradation, hence leades to
problems of physicochemical & biostability, short biological half life &problems of physicochemical & biostability, short biological half life &
inability to pass most of the biological barriers.They are used as peroralinability to pass most of the biological barriers.They are used as peroral
carriers with follo.objectivescarriers with follo.objectives
Improvement of bioavailability of drugs with poor absorptionImprovement of bioavailability of drugs with poor absorption
characteristicscharacteristics
Delivery of vaccine antigen to gut associated lymphoid tissueDelivery of vaccine antigen to gut associated lymphoid tissue
Reduction of GI irritation due to drugsReduction of GI irritation due to drugs
Assurance of stability of drugs in GI tractAssurance of stability of drugs in GI tract

58. Intra-arterial delivery of nanoparticlesIntra-arterial delivery of nanoparticles

59. The advantages of nanoparticles includes their subcellular size, targetedThe advantages of nanoparticles includes their subcellular size, targeted
surface, good suspensibility,& uniform dispersity for catheter basedsurface, good suspensibility,& uniform dispersity for catheter based
therapy & easy penetration into the arterial wall without causing traumatherapy & easy penetration into the arterial wall without causing trauma
Restenosis can be defined as the process of re-obstruction of an arteryRestenosis can be defined as the process of re-obstruction of an artery
following interventional procedures such as angioplasty, atherectomy,orfollowing interventional procedures such as angioplasty, atherectomy,or
stentingstenting
These systems are promised as carriers for genes in restenosis & otherThese systems are promised as carriers for genes in restenosis & other
gene therapy applicationsgene therapy applications
Nanoparticles are carriers for treatment of restenosis as they localizeNanoparticles are carriers for treatment of restenosis as they localize
drugs at the site of artery injury rather than systemic administrationdrugs at the site of artery injury rather than systemic administration

60. Oral delivery of nanoparticlesOral delivery of nanoparticles

61. Nanoparticles for ocular deliveryNanoparticles for ocular delivery
The short elimination half life of aq.eye drops can be extended from aThe short elimination half life of aq.eye drops can be extended from a
very short time(1-3 min) to prolonged time(15-20 min) usingvery short time(1-3 min) to prolonged time(15-20 min) using
biodegradable nanoparticlesbiodegradable nanoparticles
The efficacy of pilocarpine loaded nanoparticles is increased by coatingThe efficacy of pilocarpine loaded nanoparticles is increased by coating
them with bioadhesive & viscous polymersthem with bioadhesive & viscous polymers
Methylcellulose, PVA,HPMC for viscosity enhancing propertiesMethylcellulose, PVA,HPMC for viscosity enhancing properties
Mucin,sodium CMC,hyaluronic acid for bioadhesive propertiesMucin,sodium CMC,hyaluronic acid for bioadhesive properties

62. Nanoparticles for DNA deliveryNanoparticles for DNA delivery
Nanoparticles have been recently used as a delivery vehicle for theNanoparticles have been recently used as a delivery vehicle for the
transfection of plasmid DNA & to improve their stability in thetransfection of plasmid DNA & to improve their stability in the
bioenvironmentbioenvironment
Chitosan DNA hybrid colloidal systems either as chitosan DNA complexChitosan DNA hybrid colloidal systems either as chitosan DNA complex
or as a chitosan DNA nanospheres reported better gene expressionor as a chitosan DNA nanospheres reported better gene expression
Biodegradable & biocompatible polymer(DL-lactide-co-glycolide) wasBiodegradable & biocompatible polymer(DL-lactide-co-glycolide) was
used to encapsulate pDNA in submicron size particles. Nanosize rangeused to encapsulate pDNA in submicron size particles. Nanosize range
pDNA loaded polymer particles with high encapsulation efficiencypDNA loaded polymer particles with high encapsulation efficiency
showed sustained release of pDNA over a monthshowed sustained release of pDNA over a month

63. Nanoparticles for oligonucleotides deliveryNanoparticles for oligonucleotides delivery
Antisense agent bind to DNA or RNA sequences blocking the synthesisAntisense agent bind to DNA or RNA sequences blocking the synthesis
of cellular proteins with unparalleledof cellular proteins with unparalleled
Antisense agents are antisense sequenses or nucleotides,ribozymesAntisense agents are antisense sequenses or nucleotides,ribozymes
Antisense sequences hybridize double stranded DNA in the nucleusAntisense sequences hybridize double stranded DNA in the nucleus
forming triple helixesforming triple helixes
Riboxymes binds to single targeted mRNARiboxymes binds to single targeted mRNA
ODNs are investigated as HIV infection, Hepatitis B virus infection,ODNs are investigated as HIV infection, Hepatitis B virus infection,
Herpes simples virus, cancer, restenosis, Rheumatoid arthritis,& allergicHerpes simples virus, cancer, restenosis, Rheumatoid arthritis,& allergic
disordersdisorders

64. Various therapeutic applications of nanoparticles /nanocapsulesVarious therapeutic applications of nanoparticles /nanocapsules
ApplicationApplication MaterialMaterial PurposePurpose
Cancer therapyCancer therapy Poly(alkylcyanoacrylate)nanoparticlePoly(alkylcyanoacrylate)nanoparticle
swith anticancerswith anticancer
agents,oligonucleotidesagents,oligonucleotides
Targeting,reduced toxicity,Targeting,reduced toxicity,
enhanced uptake ofenhanced uptake of
antitumour agents,antitumour agents,
improved in vivo & in vitroimproved in vivo & in vitro
stabilitystability
IntracellularIntracellular
targetingtargeting
Poly(alkylcyanoacrylate)Poly(alkylcyanoacrylate)
Polyester nanoparticles with antiPolyester nanoparticles with anti
parasitic or antiviral agentsparasitic or antiviral agents
Target RES for intracellularTarget RES for intracellular
interactionsinteractions
Prolonged systemicProlonged systemic
circulationcirculation
Polyesters with adsorbedPolyesters with adsorbed
polyethylene glycols or pluronicspolyethylene glycols or pluronics
Prolong systemic drugProlong systemic drug
effect,avoid uptake by RESeffect,avoid uptake by RES
Vaccine adjuvantVaccine adjuvant PolyPoly
(methylmetghacrylate)nanoparticles(methylmetghacrylate)nanoparticles
with vaccines(oral & IM injection)with vaccines(oral & IM injection)
Enhances immuneEnhances immune
responseresponse

65. ApplicationApplication MaterialMaterial PurposePurpose
PeroralPeroral
absorptionabsorption
Poly(methylmetghacrylate)nanopartiPoly(methylmetghacrylate)nanoparti
cles with proteins & therap.agentscles with proteins & therap.agents
Enhanced bioavailabilityEnhanced bioavailability
&protection from GI enzymes&protection from GI enzymes
Ocular deliveryOcular delivery Poly(alkylcyanoacrylate)withPoly(alkylcyanoacrylate)with
steroids,antiinflammatorysteroids,antiinflammatory
agents,antibacterial agents foragents,antibacterial agents for
glaucomaglaucoma
Improved retention ofImproved retention of
drugs/reduced wash outdrugs/reduced wash out
DNA deliveryDNA delivery DNA gelatin nanoparticles, DNADNA gelatin nanoparticles, DNA
chitosan nanoparticles,chitosan nanoparticles,
Enhanced delivery & higherEnhanced delivery & higher
expression levelsexpression levels
OligonucleotideOligonucleotide
deliverydelivery
Alginate nanoparticles,Alginate nanoparticles,
poly(D,L)lactic acid nanoparticlespoly(D,L)lactic acid nanoparticles
Enhanced delivery ofEnhanced delivery of
oligonucleotideoligonucleotide
OtherOther
applicationsapplications
Poly(alkylcyanoacrylate)nanoparticlPoly(alkylcyanoacrylate)nanoparticl
es with peptideses with peptides
For transdermal applicationFor transdermal application
Nanooparticles with radioactive orNanooparticles with radioactive or
contrast agentscontrast agents
Copolymerized peptideCopolymerized peptide
nanoparticles of n-butylnanoparticles of n-butyl
cyanoacrylate & activated peptidescyanoacrylate & activated peptides
Crosses blood brain barrierCrosses blood brain barrier
Improved absorption & permeationImproved absorption & permeation
EnzymeEnzyme
immunoassays,Radioimagingimmunoassays,Radioimaging
Oral delivery of peptidesOral delivery of peptides