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


       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


       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


      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


      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,


      Polyisobutyl cyanoacrylate


      Serum albumin


      Polyacryl dextran

      Polyacryl starch


      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 (100oC) (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 40o C, subsequent cooling to 4O 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


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


Heated to above 650C


Oligomers aggregate & precipitates


lsolation of nanospheres

Characterization and evaluation of nanoparticles



Particle size

- Photon correlation spectroscopy

- Laser defractometry

- Scanning electron microscopy

Molecular weight

- Gel Chromatography

Charge determination

- Laser Doppler Anemometry

- Zeta potentiometer


- Helium pycnometer


- X-ray diffraction & DSC

- Thermogravimetry


- Hydrophobic interaction

- Chromatography

Surface element analysis

- X-ray

- Photo emission Spectroscopy

Specific Surface Area

Specific surface area( A) = 6/Density x diameter of particle

Invitro Release :


-Diffusion Cell

-Modified Ultra Filtration Technique.

-Media Used : Phosphate Buffer

Nanoparticle Yield :

% Yield =

Actual weight of Product        X 100 

Total weight of Drug and Excipients


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




Cancer therapy

Targeting, Reduced toxicity,  enhance uptake of anti-tumor  agent

Polyalkylcyanoacrylate with

anticancer agent

Intra cellular targeting

Target reticuloendothelial  system for intracellular  infection

Poly alkyl cyanoarylate

Vaccine adjuvant

Prolong systemic drug effect.  Enhance immune response

Poly methyl metha acrylate  nanoparticles with vaccines

DNA delivery

Enhanced bioavailability and  significantly higher expression  level

DNA gelatin nanoparticles,

DNA chitosan nanoparticles

Ocular delivery

Improved retention of the drug and reduced washed out.

Poly alkyl cyanoacrylate  nanoparticles , anti-  inflammatory agent


  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

  1. Nanoparticles can be characterized for their particle size , molecular  weight, surface charge, surface texture, density, crystallinity,  hydrophobicity, surface area, drug release and drug entrapment
  2. The polymers used can be synthetic or natural polymers
  3. Nanoparticles can be Metal-based, Lipid-based or Polymer-based in nature
  1. 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)

  1. 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)

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