NOVEL DRUG DELIVERY SYSTEMS (BP 704T ) Unit 4

This subject is designed to impart basic knowledge on the area of novel drug delivery systems.

2. •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.

•It is a method of delivering medication to a patient in a manner that increases the
concentration of the medication in some parts of the body relative to others.

•Targeted drug delivery seeks to concentrate the medication in the tissues of interest while
reducing the relative concentration of the medication in the remaining tissues.

•This improves efficacy and reduce side effects

3. REASON FOR DRUG TARGETING
•In the treatment or prevention or diseases.
•Drug instability
•Short half life
•Low therapeutic index
•Low absorption
•Large volume of distribution
•Low specificity

4. Component of targeted Drug delivery
1.Target
•Target means specific organ or a cell or group of cell which in chronic or acute condition need
treatment

2.Carrier or marker
•Carrier is one of the special molecule or System essentially require for effective
transportation of loaded drug up to the pre selected sites

3. Drug

5. Approaches of TDDS
1.Controlling the distribution of drugs by incorporating it in a carrier system

2.Altering the structure of the drug at molecular level

3.Controlling the input of the drug into bio-environment to ensure a programmed and
desirable bio distribution

6. IDEAL CHARACTERISTICS
•It should be nontoxic, biocompatible, biodegradable.

•Restrict drug distribution to target cells or tissues or organs and should have uniform capillary
distribution.

•Controllable and predicate rate of drug release.

•Drug release does not effect the drug action.

•To control therapeutic amount of drug release.

•Minimal drug leakage during transit.

•Carriers used must be bio-degradable or readily eliminated from the body without any
problem and no-carrier induced modulation of diseased state.

•The preparation of the delivery system should be easy or reasonably simple, reproductive
and cost effective.

7. ADVANTAGES:
•Dose is less compared to conventional drug delivery system.

•Drug administration protocols may be simplified.

•Toxicity is reduced by delivering a drug to its target site, there by reducing harmful systemic
effects.

•Drug can be administered in a smaller dose to produce the desire effect.

•Improved bioavailability

•Avoidance of hepatic first pass metabolism.

•Reduced dosing frequency

•No peak and valley plasma concentration.

•Selective targeting to infections cells that compare to normal cells.

8. DISADVANTAGES
•Rapid clearance of targeted systems.

•High cost of final product

•Immune reactions against intravenous administered carrier systems.

•Insufficient localization of targeted systems into tumor cells.

•Patient discomfort with device usage

•Requires highly sophisticated technology for the formulation.

•Requires skill for manufacturing storage, administration.

•Drug deposition at the target site may produce toxicity symptoms.

•Difficult to maintain stability of dosage form.
E.g.: Resealed erythrocytes have to be stored at 4º С.

9. STRATEGIES OF DRUG TARGETING
1)Passive Targeting:
•Drug delivery systems which are targeted to systemic circulation are characterized as Passive
delivery systems.

•In this technique drug targeting occurs because of the body's natural response to
physicochemical characteristics of the drug or drug carrier system.

2) Inverse Targeting :
•In this type of targeting attempts are made to avoid passive uptake of colloidal carrier by RES
(Reticulo endothelial Systems) and hence the process is referred to as inverse targeting.

3)Active Targeting:
•In this approach carrier system bearing drug reaches to specific site on the basis of
modification made on its surface rather than natural uptake by RES (Reticulo endothelial
Systems).

10. 4) Physical Targeting:
•In this type of targeting some characteristics of environment changes like pH, temperature,
light intensity, electric field, ionic strength small and even specific stimuli like glucose
concentration are used to localize the drug carrier to predetermined site.

5) Dual Targeting:
•In this targeting approach carrier molecule itself have their own therapeutic activity and thus
increase the therapeutic effect of drug.

6) Double Targeting:
•Temporal and spatial methodologies are combined to target a carrier system, then targeting
may be called double targeting.

11. LIPOSOME
•Liposomes are microscopic spheres made from fatty material

•Liposomes are spherical vesicles having an aqueous
Core enclosed by one or more phospholipid bilayer

•Concentric bilayer vesicles

•In which an aqueous volume is entirely enclosed
By a membrane lipid bilayer

•Lipid bilayer is mainly composed of natural or
Synthetic phospholipid

•Liposomes are derived from Greek word
Lipo means Fatty constituents
Soma means structure

12. Formulation/ Composition of Liposomes
1)Phospholipid -
•It is the major component of the biological membrane two types of
phospholipids are used natural and synthetic phospholipids.

•The most common natural phospholipid is the Phosphatidylcholine (PC).

•Hence have affinity for both hydrophilic drug can be encapsulated in the
aqueous phase and hydrophilic molecule can be incorporated in the lipid
bilayer

•It is originated from animal (hen egg) and vegetable (soya bean).

2) Cholesterol -
•it is useful in stabilizing the membrane
•Decide shape, penetration power.
•It can interdigitated in the phospholipid

13. Based on their size and number of bilayers liposomes are classified into three basic types:-
1.Multilamellar Vesicles (MLVs)
•These liposomes have more than one lamella and their size between 300-5000nm

2.Large Unilamellar Vesicles (LUVs)
•These liposomes have single lamella and their size range from 100 nm to 300 nm

3.Small Unilamellar Vesicles (SUVs)
•These liposomes have single lamella and are smaller than 20 nm to 100 nm

15. Method of preparation of liposomes
1)Mechanical Dispersion Method
2)Solvent Dispersion Methods
3)Detergent Removal Methods

1.Mechanical Dispersion Method
Lipid dissolve in organic solvent and add Aqueous solvent

Remove organic solvent under rotary vacuum evaporator

Film deposition

Solid liquid mixture is hydrated by using aqueous buffer (high speed stirring)

Liquid spontaneously swell

Liposome prepare



Examples
•Lipid film hydration
•Micro emulsification
•Sonification
•Dried reconstitute vesicle

16. 2.Solvent Dispersion Methods
Lipid dissolve in organic solvent

Excess addition of aqueous phase containing material is to be entrapped in liposomes under
rapid dilution(Rapid evaporation of organic phase)

Formation of monolayer bilayer of phospholipids

Liposomes prepare

Examples
•Ethanol injection
•Ether injection
•De emulsification

17. 3.Detergent Removal Methods
Phospholipid brought into intimate contact with aqueous phase with the help of detergent
(Surfactant)

Detergent remove by dialysis

Formation of liposomes

Example
•Dilution
•Column
•chromatography

18. Advantages of Liposomes
•Liposomes are biocompatible, completely biodegradable, non-toxic, flexible and non-
immunogenic for systemic and non-systemic administration.

•Provide selectively passive targeting to tumor tissue

•Liposomes have ability to protect their encapsulated drug from the external environment and
to act as sustained release depots.

•They alter pharmacokinetic and pharmacodynamic properties of drug

•Liposomes can be formulated as a suspension, as an aerosol, or in a semisolid form such as
gel, creamed lotion, as a dry vesicular powder.

•They can be administered through most routes of administration including ocular,
pulmonary, nasal, oral, intramuscular, subcutaneous and intravenous.

•Liposomes are increased efficacy and therapeutic index of drug

19. Disadvantages of Liposomes
•Production cost is high.
•Leakage and fusion of encapsulated drug.
•Sometimes phospholipid undergoes oxidation and hydrolysis like reaction.
•Short half-life.
Applications
•Provide controlled and sustained release
•They are use in antimicrobial, antifungal, and antiviral therapy
•Used in tumour therapy
•Used in gene therapy and immunology
•Cosmetics and dermatology
•Radiopharmaceuticals

20. NIOSOMES

•Niosomes are a novel drug delivery system in which the
drug medication is encapsulation in a vesicle.

•The vesicle is composed of a bilayer of non-ionic
surfactant (Detergent)

•Niosomes are either unilamellar or multilamellar,
depending on their preparation methods.

•These vesicular system are similar to liposome

•have affinity for both hydrophilic drug can be encapsulated in the
aqueous phase and hydrophilic molecule can be incorporated in the lipid
bilayer

21. General Characteristics
•Noisomes are biodegradable, biocompatible, non-toxic, non-immunogenic and non-
carcinogenic.

•Non-ionic surfactant bilayer formation is based on HLB value (Hydrophilic lipophilic balance)
of the surfactant, the chemical structure of the component.

•Properties of niosomes depends on composition of bilayer and method of preparation.

22. Component of Niosomes :-
1.Non-ionic surfactant
•Selection of surfactant should be done on the basis of HLB value.

Ex: polyglycerols alkyl ether, crown ethers, glucosyl dialky ether, ester linked surfactant etc.

2. Cholesterol
•Is used to provide rigidity and proper shape.

•cholesterol is a steroid derivatives.

3.Charged inducing molecule
•Some charged molecules are added to niosomes to increase stability of niosomes by
electrostatic repulsion.( To prevent aggregation of Niosome)

•The negatively charged molecule used are diacetyl phosphate and phosphatidic.

•Positively Charged molecule are stearyl amine.

23. Types
1)Small Unilamellar Vesicles (SUVs):
•Single layer and size of these vesicles (10-100nm)

2)Multi-Lamellar Vesicles (MLVs):
•They are prepared by hand-shaking method.
•One or more surfactant layer present (>1 Bilayer)

3)Large Unilamellar Vesicles (LUVs):
•Single layer vesicles and size of these vesicles (100-3000nm)

24. Methods of preparation of Niosomes
Common stages of all methods of preparation of Niosomes
Cholesterol and Non ionic surfactant

Dissolve in organic Solvent

Solution in organic Solvent

Drying

Thin film

Dispersion (Hydration) Remove of water

Niosomes suspension

25. 1)Ether injection methods
2)Hand shaking methods
3)Reverse phase evaporation
4)Sonication
5)Multimembrane extension method

1.Ether injection methods
Surfactant + cholesterol added in ether solution is dissolved.

Ether slowly injected into pre-heated aqueous solution of drug maintained at 60 °c.

Vaporization of ether leads to formation of unilamellar

LUVs niosomes

26. 2.Hand shaking method
Surfactant & cholesterol is dissolved in 10ml ether in round bottom flask.(Hand Shaking)

Ether is evaporated under vacuum at room temperature using rotary evaporator.

Surfactant swells and peeled off into a film like lipid.

Formation of niosomes

3. Sonication
Surfactant + Cholesterol mixture is dispersed in 2 ml of aqueous phase in vial

Mixture is sonicated for 10 min at 60°c using titanium probe sonication (Sound energy)

Formation of unilamellar niosomes.

28. 5.Multiple membrane extrusion Method
Mixture of surfactant, cholesterol & diacetyl phosphate in chloroform.

Then solvent is evaporate using rotary vacuum evaporator to leave thin film

The film is hydrated with aqueous drug solution and the resultant suspension.

Obtained uniform size of niosomes

29. Advantages
•Using niosome the drug is delivered directly to the body
•Decreased the side effect
•Improved therapeutic efficacy of the drug
•Improved bioavailability
•Enhanced the skin permeability
•Storage, handling transportation is easy
•More stable than liposomes
Disadvantages
•They have a low solubility
•Short half life
•Production cost is high

30. Applications of Niosomes
•Better patient compliance and therapeutic effect than conventional formulations.

•Show controlled and sustained release of drugs.

•Effectively used in targeting of drugs.

•It can be used in ocular drug delivery with no tissue irritation and damage by penetration
enhancers.

•To improve efficacy of drugs in cancer therapy.

•In diagnostic imaging with carrier radio pharmaceutics.

•Cosmetics

31. NANOPARTICLES
•Nanoparticle are 1 nm to 100 nm in size.

•Nano derives from the Greek word "nanos", which means extremely small.

•Nanoparticle are sub-nanosized colloidal structure composed of synthetic or semi-synthetic
polymer.

•The drug may be added during the preparation of nanoparticles.

On the basis of their preparation nanoparticle are of the two type
1.Nanospheres - Matrix type structure in which a
Drug is dispersed

2. Nanocapsules - Membrane wall structure with an core
containing Drug

32. Advantages
•They can be administered through various route including oral, nasal, parenteral, intraocular
•Nanoparticle drug carriers have higher stabilities
•Nanoparticles have higher carrier capacity
•Feasibility of incorporation of both hydrophilic and hydrophobic substances
•Feasibility of variable routes of administration
•Capable of being stored for longer periods.
•Nanoparticles can also be used for controlled delivery of drugs
•Nanoparticles reduces dosing frequency and have higher
•Good bioavailability
•Nanoparticle are biodegradable.

33. Disadvantages
•Polymeric nanoparticles posses limited drug-loading capacity

•On repeated administration, toxic metabolites may be formed during the biotransformation
of polymeric carriers.

•The polymeric nanoparticles are relatively slowly biodegradable which might cause systemic
toxicity.

•High cost

•Reduced ability to adjust does

•Required skill to manufacture

34. Methods used for nanoparticle preparation
1.Salting out method
Aqueous phase Organic phase
(surfactant and Electrolyte) solvent (Acetone) and polymer
(Emulsification)
O/W emulsion
Dilution with distilled water
Nanoparticles

35. 2.Solvent emulsification evaporation method
Polymer + Drug

Dissolve in water immiscible organic solvent (Chloroform)

Pour with emulsifier coating aqueous phase

O/W Emulsion (Nanodroplets)

Homogenization or sonication

Continuous mild stirring at room temperature

Nanosuspension

Ultracentrifugation Washing Freeze drying

Nano particles

36. Applications
•Widely used in case of cancer therapy
•Use in intracellular targeting
•Used in DNA delivery
•Use in ocular delivery
•Help to deliver drug across the blood brain barrier
•Controlled and sustained release formulation

37. MONOCLONAL ANTIBODIES
•Hybridoma technology method used to produce monoclonal antibodies

•An antibody is a protein used by the immune system to identify and neutralize foreign
objects like bacteria and viruses.

•Each antibody recognizes a specific antigen unique to its target.

•Each antibody with a specific antigen

•Antibodies have high specificity towards target, drugs, serum, microorganism

•Antibodies used to precipitate soluble antigen clumps cells and kill bacteria

•Antibodies are produced from a special type of group of cell called B-lymphocytes

•An antibodies combines to some particular types of antigen called epitopes

38. Methods of preparation of monoclonal
antibodies
•HAT Medium
(hypoxanthine-aminopterin-thymidine medium)

39. Practical Steps for Production
1.Immunize animal (Antigen)
2.Isolate spleen cells (containing antibody - produced B-cell).
3.Fuse spleen cells with myeloma cells.
4.Allow unfused B-cells to die.
5.Add aminopterin to culture and kill unfused myeloma cells.
6.Screen supernatant of each clone for presence of desired antibody.
7.Grow chosen clone of cells in tissue culture indefinitely.
8.Harvest antibody from the culture

40. Advantages
•Cheap to develop than conventional drugs
•Adverse drug reaction can be reduce
•They affect the affected cell and not the unaffected cell
•They have wide range of treating condition

Disadvantages
•Needs specialized tools and personal to formulate monoclonal antibodies
•Culture can lead to contaminated
•Can be used for limited animals
•Take more time to production of monoclonal antibodies

41. Applications of Monoclonal Antibodies
Diagnostic Applications
•Cardiovascular diseases
•Deep vein thrombosis
•Immunosuppressive therapy
•Pregnancy testing kits

Therapeutic Applications
•Radioisotope
•Toxin and drug immunoconjugates
•Immunoliposome based kits
•In cancer
•Used in treatment of AIDs