Nanoparticles

Nanoparticles

Targeted
drug delivery systems

Session objectives

By the end of this session, students will be able to:

•       Explain
the importance of nanoparticles

•       Explain
the advantages and limitations of
nanoparticles

•       Describe
different methods used for preparation of nanoparticles

•       Describe
the applications of nanoparticles

•       Explain
the methods used for the characterization of nanoparticles

Definitions

•       Nanosuspensions
:

–      Are
colloidal dispersions of nano sized drug particle that are produced by suitable method and stabilized by
suitable stabilizer

•       Nanoparticles
:

–      They
are solid colloidal particles sized from 1-1000 
nm

•       Nanospheres
:

–      Polymer
matrices in which drug is dissolved or dispersed

•       Nanocapsules
:

–      Consists
of polymer wall entrapping an oily core in which the drug is dissolved

Introduction

•       Nanoparticles
are subnanosized colloidal drug delivery 
systems ranging in size from 10-1000 nm in diameter

•       They
are composed of synthetic or semi-synthetic polymers carrying drugs or
proteinaceous substances, i.e. 
antigen(s)

•       Drugs
are entrapped in the polymer matrix particulates or  solid solutions or may be bound to particle
surface by  physical adsorption or in
chemical form

Types of nanoparticles

•       Monolithic
type

•       Capsule
type

Importance of nanoparticles

•      Selective
and Effective Localization of pharmacologically 
active moiety at preselected target(s) in
therapeutic  concentration

•      Restricted
access to non-target normal tissues and cells.

•      Nanoparticles
are mainly taken by the RES after the 
administration and are useful to carry drugs to the liver and  to cells that are phagocytically active

•      By
modifying the surface characteristics of the 
nanoparticles it is possible to enhance the delivery of drugs  to spleen relative to the liver

•      Distribution
of the nanoparticles in the body may be 
achieved possibly by : Coating of nanoparticles with  certain Serum components, Attachment of
antibodies  or sulfoxide groups and the
use of Magnetic  nanoparticles

Advantages

•      Reduction
in the frequency of the dosages taken by 
the patient

•      More
uniform effect of the drug

•      Reduction
of drug Side Effects

•      Reduced
fluctuation in circulating drug levels

•      Avoids
hepatic first pass metabolism

Disadvantages

•      High cost

•      Productivity
more difficult

•      Reduced
ability to adjust the dose

•      Highly sophisticated
technology

•      Requires
skills to manufacture

•      Difficult
to maintain stability of dosage form

Ideal characteristics

•      It should be
biochemical inert, non-toxic and non-immunogenic

•      It should
be stable both physically and chemically in In vivo & in vitro conditions

•      Restrict
drug distribution to non-target cells or tissues or organs & should have
uniform  distribution

•      Controllable
& Predicate rate of drug release

•      Drug
release should not effect drug action

•      Specific Therapeutic
amount  of drug release must be possessed

•      Carriers used
must be biodegradable or readily eliminated from the body without any problem

•      The  preparation 
of the delivery system should be easy or reasonable

•      Simple,
reproducible & cost effective

Polymers used

•      Polymethyl
methacrylate copolymers,

•      Polymethyl
cyanoacrylate,

•      Polybutyl
cyanoacrylate & Polyisobutyl cyanoacrylate,

•      Polyhexyl
cyanoacrylate & polyisohexyl cyanoacrylate,

•      Poly(Nα,NÎ-L-lysinedylterephthalamide

•      Polyisobutyl
cyanoacrylate

•      Poly-D,L-lactide

•      Serum
albumin

•      Gelatin

•      Polyacryl
dextran

•      Polyacryl
starch

•      Albumin

•      Polylactic
acid-poly glycolic acid copolymer

•      Poly(b-hydroxy
butyrate)

•      Ethyl
cellulose

•      Eudragit
RL,RS

Methods of preparation

A. Cross Linking Methods

1)      By
Cross-linking of Amphiphilic Macromolecules

2)      By Crosslinking
in W/O Emulsion

3)      By Emulsion
chemical dehydration

4)      By Phase
Separation

5)      By pH
lnduced Aggregation 

B. Polymerization Methods

1)      Emulsion
polymerization

2)      Dispersion
polymerization

1) By
Cross-linking of amphiphilic macromolecules

•       Nanoparticles  can be  prepared
from Amphiphilic macromolecules, proteins and polysaccharides (which have  affinity for aqueous and lipid solvents)

•       The
method involves Aggregation of Amphiphiles followed  by stabilization either by heat denaturation
or chemical  cross-linking

2) By Cross linking in
W/O emulsion

•       Emulsification
of bovine serum albumin (BSA) or human 
serum albumin (HSA) or protein aqueous solution in oil  using high-pressure homogenization or high
frequency  sonication

•      Emulsification using high- 
pressure homogenization or high frequency sonication

W/O emulsion

•      Dilution with preheated oil (100^oC) (Heat cross-linking) or Addition of crosslinking agent (Chemical
cross-linking)

•      Centrifugation and isolation of 
nanoparticles

3) Emulsion chemical
dehydration

•      Stabilization
can also be achieved by emulsion chemical 
dehydration

•      Hydroxy
propylcellulose solution in chloroform is used 
as a continuous phase, while a chemical dehydrating  agent,

•      2,2,
di-methyl propane is used to disperse into the 
internal aqueous phase to form an Emulsion

•      This method
avoids coalescence of droplets and could 
produce nanoparticles of smaller size (300nm)

4) Phase seperation

•      The protein
or polysaccharide from an aqueous phase can 
be Desolvated by :

a)      pH change

b)      Change in
temperature

c)      Addition of
appropriate counter ions e.g. alginate

Aqueous
phase (protein aqueous solution)

Heat to 40^o
C, subsequent cooling to 4^O C for 24h.  â  Desolvation

Protein
aggregates (Coacervates)

â Resolvation

Protein
colloidal dispersion

â Cross-linking

Nanoparticles
dispersion (External aqueous phase) 200nm

5) pH induced aggregation

•      Gelatin
Nanospheres were prepared by :

•      Gelatin
& tween 20 were dissolved in aq. phase & pH of the solution was
adjusted to optimum value.

•      The clear
solution so obtained was heated to 40⁰C followed by its quenching at
4⁰C for 24hrs & subsequently left at ambient temperature for
48hrs.

•      The
sequential temperature treatment resulted into a colloidal dispersion of
aggregated gelatin. The aggregates were finally cross  linked using glutaraldehyde as cross linking
agent the optimum pH  was 5.5- 6.5.values

•      pH below
5.5 produced no aggregation while above 6.5 an 
uncontrolled aggregation led to the formation of larger nanospheres

Polymerization based methods

1)      Emulsion polymerization :

It consists of:

a)      Micellar nucleation and polymerization :

Monomer is
insoluble in continuous phase-(O/W phase) – Aqueous phase 

b)     Homogenous nucleation and polymerization :

Monomer is soluble in continuous phase- (W/O phase) – Organic
phase

2] Dispersion polymerization

(Acrylamide
or Methyl methacrylate) Monomer is dissolved in an aqueous medium

â

Further, by
chemical initiation (ammonium or potassium per oxo disulphate)

â

Heated to
above 65⁰C

â

Oligomers
aggregate & precipitates

â

lsolation
of nanospheres

Characterization and evaluation
of nanoparticles

Applications

1)      Cancer
Therapy

2)      In
lntracellular Targeting

3)      Used for
Prolonged Systemic Circulation

4)      As a
Vaccine    Adjuvant

5)      In Case of
Ocular delivery

6)      Used in DNA
Delivery

7)      It is used
in case of Oligonucleotide delivery

8)      Enzyme
immunoassays

9)      Radio-imaging

10)  To cross BBB

Summary

1. Nanoparticles  are subnanosized colloidal drug delivery systems  ranging in size from 10-1000 nm in
   diameter
2. Selective
   and Effective Localization of drug  to
   target sites
3. The
   methods of preparation include 

A. Cross
Linking Methods

1)      By
Cross-linking of Amphiphilic Macromolecules

2)      By Cross-linking
in W/O Emulsion

3)      By Emulsion
chemical dehydration

4)      By Phase
Separation

5)      By pH
lnduced Aggregation 

      B. Polymerization Methods

                   1) Emulsion
polymerization

                   2)
Dispersion polymerization

4. Nanoparticles
   can be characterized for their particle size , molecular  weight, surface charge, surface texture,
   density, crystallinity, 
   hydrophobicity, surface area, drug release and drug entrapment
5. The
   polymers used can be synthetic or natural polymers
6. Nanoparticles
   can be Metal-based, Lipid-based or Polymer-based in nature

7. Carbon
   nanotubes (CNTs) are allotropes of carbon, made of graphite  and constructed in cylindrical tubes
   with nanometer in diameter and 
   several millimeters in length

             Based on the number of layers,
structures of CNTs are classified into two types:

             – Single-walled
Carbon Nanotubes (SWCNTs)

             –
Multi-walled Carbon Nanotubes (MWCNTs)

8. Three
   main techniques used for SWCNTs and MWCNTs production are

1)      Arc-Discharge
method (using arc vaporization of two carbon rods)

2)      Laser
Ablation method (using graphite)

3)      Chemical
Vapor Deposition (using hydrocarbon sources such as CO,  methane, ethylene, acetylene)

  Detailed Image Based Notes Click on Download Button