Nanoparticles- Definition, Adv, Preparation methods(solvent evaporation, solvent diffusion, nanoprecipitation, ionic gelation, polymerization,salting out etc),Evaluation (particle size, percentage yield, zeta potential,SEM,TEM, Drug entraptment etc) and Applications

1. TARGET ORIENTED DRUG DELIVERY
SYSTEM:
NANOPARTICLES
PRESENTED BY:
JYOTI NAUTIYAL
M.PHARM – PHARMACEUTICS
2ND YEAR
SGRRITS

2. INTRODUCTION
 Targeted drug delivery system is a special form of drug delivery system where
the 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.

3. NANOPARTICLES
“ Nanoparticles are nanosized colloidal structures composed of synthetic or semi-
synthetic polymers.”
 Size range : 10–1000 nm
 The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle
matrix.
 The first reported nanoparticles were based on non-biodegradable polymeric
system that is polyacrylamide, polymethyl methacrylate, polysterene etc. by
Birrenbach and Speiser , 1976 ; Kreuter and Speiser , 1976.

5. ADVANTAGES
 Nanoparticles can act as controlled release system depending on their
polymeric composition.
 Less amount of dose required.
 They enhance aqueous solubility of poorly soluble drug therefore increase its
bioavailability, therapeutic efficacy and
 Reduces side effects.
 Nanoparticles can be administer by various routes including oral, nasal,
parenteral, intra-ocular etc.
 As a targeted drug carrier nanoparticles reduce drug toxicity.

6. POLYMERS USED IN PREPARATION OF
NANOPARTICLES
NATURAL POLYMERS SYNTHETIC POLYMER
• Gelatin
• Albumin
• Lectins
• Alginate
• Dextran
• Chitosan
• Agarose
• Poly( e-caprolactone)(PECL)
• Poly(lactic acid) (PLA)
• Poly (lactide-co-glycolide) (PLGA)
• Polystyrene
• Poly (isobutyl cyano acrylate) (PICA)
• Poly (butyl cyano acrylate) (PBCA)
• Polyhexyl cyano acrylate(PHCA)
• Poly methyl (methacrylate) (PMMA)

7. PREPARATION TECHNIQUES
Methods for
preparation of
nanoparticles
Polymer precipitation
method
Solvent evaporation
Emulsification/solvent
diffusion
Nanoprecipitation
Polymerization based
methods
Emulsion
polymerization
Interfacial
polymerization

8. SOLVENT EVAPORATION
Polymer and drug is dissolved in an organic solvent such as dichloromethane,
chloroform or ethyl acetate.
The mixture of polymer and drug solution is then emulsified in an aqueous
solution containing a surfactant or emulsifying agent to form an oil in water
(o/w) emulsion.
After the formation of stable emulsion, the organic solvent is evaporated either
by reducing the pressure or by continuous stirring.
Nanoparticles

10. NANOPRECIPITATION
Polymers, drug, and or lipophilic surfactant are dissolved in a water miscible
solvent such as acetone or ethanol.
The solution is then poured or injected into an aqueous solution containing
stabilizer under magnetic stirring.
Nano particles are formed instantaneously by the rapid solvent diffusion(Polymer
deposition on the interface between the water and the organic solvent, caused by
fast diffusion of the solvent)
Nanoparticles were separated by using cooling centrifuge

12. CONT.
 This method is useful for drugs that are slightly soluble in water.
 If the drug is highly hydrophilic, it diffuses out into external aqueous phase as
nanocrystals, which further grow during storage.

13. SOLVENT DIFFUSION METHOD
 This method is developed from solvent evaporation method. The
encapsulating polymer is dissolved in a partially water soluble solvent
such as propylene carbonate and saturated with water to ensure the initial
thermodynamic equilibrium of both liquids.
 Subsequently, the polymer-water saturated solvent phase is emulsified in
an aqueous solution containing stabilizer, leading to solvent diffusion to
the external phase and the formation of nanospheres or nanocapsules.
 Finally, the solvent is eliminated by evaporation or filtration.

14. IONIC GELATION OR COACERVATION
 Polymeric nanoparticles are prepared by using biodegradable hydrophilic
polymers such as chitosan, gelatin and sodium alginate.
 The method involves a mixture of two aqueous phases, of which one is the
polymer chitosan, a di-block co-polymer ethylene oxide or propylene oxide
(PEO-PPO) and the other is a poly anion sodium tripolyphosphate (TPP).

15. CONT.
Cationic solution of chitosan dissolved in diluted acetic acid and Anionic
solution of TPP was dissolved in distilled water
TPP solution was added drop-wise into the cationic solution of chitosan
Mechanical stirring
Chitosan Nanoparticles were formed

16. CONT.
 In this method, positively charged amino group of chitosan interacts with
negative charged tripolyphosphate to form coacervates with a size in the
range of nanometer.

17. SALTING OUT
• Salting out is based on the
separation of a water-miscible
solvent from aqueous solution via a
salting-out effect.
• Polymer and drug are initially
dissolved in a solvent which is
subsequently emulsified into an
aqueous gel containing the salting
out agent (electrolytes, such as
magnesium chloride and calcium
chloride, or non- electrolytes such as
sucrose) and a colloidal stabilizer
such as polyvinylpyrrolidone (PVP) or

18. CONT.
 This oil/water emulsion is diluted with a sufficient volume of water or
aqueous solution to enhance the diffusion of solvent into the aqueous phase,
thus inducing the formation of nanospheres.
 It is different from nanoprecipitation method as in nanoprecipitation
polymeric solution is completely miscible with the external phase. But in this
method the miscibility of both the phase is prevented by the saturation of
external aqueous phase with PVA and Magnesium chloride.

19. EMULSION POLYMERIZATION
 In this the monomer is dissolved in a continuous phase that is usually an
aqueous solution, and the surfactants or emulsifiers are not needed.
 The polymerization process can be initiated by different mechanisms. Initiation
occurs when a monomer molecule dissolved in the continuous phase, collides
with an initiator molecule that might be an ion or a free radical.
 Initiator which generates either radicals or ions depending upon the type of
initiator and starts polymerization process.

20. CONT.
 Alternatively, the monomer molecule can be transformed into an initiating
radical by high-energy radiation, including g-radiation, or ultraviolet or
strong visible light. Chain growth starts when initiated monomer ions or
monomer radicals collide with other monomer molecules according to an
anionic polymerization mechanism .
 Phase separation and formation of solid particles can take place before or
after termination of the polymerization reaction.

21. INTERFACIAL POLYMERIZATION
 It is one of the well-established methods used for the preparation of
polymer nanoparticles.
 It involves two steps-
 Polymerization of two reactive monomers or agents, which are dissolved
respectively in two phases (i.e., continuous- and dispersed-phase)
 The reaction takes place at the interface of the two liquids.
 Nanometer-sized hollow polymer particles were synthesized by employing
interfacial cross-linking reactions as polyaddition and polycondensation or
radical polymerization. Oil-containing nanocapsules were obtained by the
polymerization of monomers at the oil/water interface of a very fine oil-in-
water micro- emulsion.

24. EVALUATION OF NANOPARTICLES
 Yield of Nanoparticles
The yield of nanoparticles was determined by comparing the whole weight of
nanoparticles formed against the combined weight of the copolymer and drug.
 Particle size
Particle size and size distribution are the most important characteristics of nanoparticle
systems. Currently, the faster and most routine method of determining particle size is by
Dynamic Light Scattering.
 Particle Shape
Surface morphology study carried out by Scanning Electron Microscopy (SEM) of
prepared nanoparticle.

25. CONT.
 Polydispersity index
Polydispersity index of prepared nanoparticles was carried out by using Malvern
Zetasizer. Polydispersity is index of variation within the particle size distribution.
 Zeta potential
The Zeta potential of a nanoparticle is commonly used to characterized the
surface charge property of nanoparticles. It reflects the electrical potential of
particles and is influenced by the composition of the particle and the medium
in which it is dispersed. Nanoparticles with a zeta potential above (±) 30 mV
have been shown to be stable in suspension, as the surface charge prevents
aggregation of the particles.

26.  Drug Entrapmaent Efficiency
The nanoparticles were separated from the aqueous medium by
ultracentrifugation at 10,000 rpm for 30 min. Then the resulting supernatant
solution was decanted and dispersed into phosphate buffer saline pH 7.4. The
amount of drug present in clear supernatant after centrifugation for 30 min at
10,000 rpm was determined by UV spectroscopy. The amount of drug in
supernatant was then subtracted from the total amount of drug added during
preparation of nanoparticle (W).
CONT.

28. NANOPARTICLES FOR CENTRAL NERVOUS
SYSTEM
 Entry of a molecule into the brain is mainly governed by blood brain barrier
(BBB) which is a highly selective semipermeable membrane barrier that only
allow passage of molecules with high o/w partition coefficient.
 Research has been going on to discover methods to cross this BBB, one of
which is using nanoparticle as drug carrier system.
 Nanoparticles can be used as an efficient tool to enhance delivery of drug to
brain. However, mechanism behind the entry of drug into the brain by
crossing BBB is still not clear. Several hypotheses are being proposed for it.

29.  Loosened tight junctions (TJ) allow the cross of NP through the BBB, either by
the presence of a surfactant in NP able to disrupt the TJ or by BBB impairment
due to pathological conditions.
 Receptor mediated transcytosis is the most common type of transport for NP
entry into the brain.
 NP + ligands (such as insulin, transferrin, lactoferrin or antibodies against
some endothelial receptors), or surfactants like the polysorbate 80 (that
adsorbs plasma proteins, namely apolipoprotrein E enabling their binding to
the lipoprotein receptor-related proteins (LRP)).

30.  The interaction between NP
ligands and respective
receptors in the endothelial cell
(luminal side) surface triggers
plasma membrane
invaginations followed by
pinch free forming vesicles,
which facilitates the release of
the NP in the opposite site of
the membrane (parenchymal
side).

31. CANCER TREATMENT
• CytImmune has published the preliminary results of a phase 1 clinical trial of
a targeted chemotherapy treatment method.
• They use gold nanoparticles attached to a molecule of a tumor-killing agent
called tumor necrosis factor alpha (TNF) as well as a molecule of Thiol-
derivatized polyethylene glycol (PEG-THIOL), which hides the TNF bearing
nanoparticle from the immune system. The PEG-THIOL allows the
nanoparticle to flow through the blood stream without being attacked.
• The nanoparticle carrying the TNF tends to accumulate in cancer tumors
but does not appear to accumulate in other regions of the body, which
limits the toxic effects of TNF on healthy cells

33. OTHER
 Abraxane, is albumin bound paclitaxel, a nano particle used for treatment
lung cancer.
 Nano particles are used to deliver the drug with enhanced effectiveness for
treatment for head and neck cancer, in mice model study ,which was carried
out at from Rice University and University of Texas MD Anderson Cancer
Center.
 Antibiotic resistance can be decreased by use of nano particles in
combination therapy. Zinc Oxide nano particles can decrease the antibiotic
resistance and enhance the antibacterial activity of Ciprofloxacin against
microorganism, by interfering with various proteins that are interacting in the
antibiotic resistance or pharmacologic mechanisms of drugs