1. Niosomes and pharmacosomes
Under the esteemed guidance of
Mrs.Yasmin begum(M.Pharm, Ph.D)
Presentation by
P.Soujanya
256212886026
M.Pharm(pharmaceutics)
Mallareddy College of Pharmacy

2. CONTENTS OF NIOSOMES
 INTRODUCTION
 STRUCTURE OF NIOSOMES
 ADVANTAGES
 MECHANISM OF NIOSOMES
 FORMULATION
 CHARACTERIZATION
 EVALUATION
 THERAPEUTIC APPLICATIONS
 MARKETED PRODUCTS

3. INTRODUCTION
• Niosomes are non-ionic surfactant vesicles obtained
on hydration of synthetic nonionic surfactants, with
or without incorporation of cholesterol or other
lipids.
• They are vesicular systems similar to liposomes that
can be used as carriers of amphiphilic and lipophilic
drugs
• These are less toxic and improves the therapeutic
index of drug by restricting its action to target cells

4. • Niosomes are a novel drug delivery system, in which the
medication is encapsulated in a vesicle.
• The niosomes are very small, and microscopic in size. Their size
lies in the nanometric scale.
• Niosomes are unilamellar or multilamellar vesicles.The vesicle is
composed of a bilayer of non-ionic surface active agents and
hence the name niosomes.
• A diverse range of materials have been used to form niosomes
such as sucrose ester surfactants and polyoxyethylene alkyl ether
surfactants, alkyl ester, alkyl amides, fatty acids and amino acid
compound.

5. Structure of Niosomes
• Niosomes are microscopic lamellar structures which are formed on
the admixture of non-ionic surfactant of the alkyl or dialkyl
polyglycerol ether class and cholesterol with subsequent hydration in
aqueous media.
• The bilayer in the case of niosomes is made up of non-ionic surface
active agents rather than phospholipids as seen in the case of
liposome.
• The niosome is made of a surfactant bilayer with its hydrophilic ends
exposed on the outside and inside of the vesicle, while the
hydrophobic chains face each other within the bilayer.

7. • Examples of non ionic surfactants used in the
preparation of niosomes :
1.Sorbitan alkyl ester (spans)
2.Polyoxyethylene glycol Sorbitan alkyl ester
(polysorbates)
3.Polyoxyethylene glycol alkyl ether (Brij)
4.Fatty alcohols example cetyl alcohol , stearyl alcohol
5.Glycerol alkyl ester example glyceryl laurate

8. • Bilayer formation :
Hydrophobic chains of surfactants are responsible for bilayer formation.
It is explained by critical packaging parameter for surfactants Pc. It is
given by
Pc = v/ao.lc
• the minimum interfacial area occupied by the head group- ao;
• the volume of the hydrophobic tail (s)- v;
• the maximum extended chain length of the tail in the micelle core-lc.
If Pc is < 0.33 the expected aggregate structure is spherical micelles.
If Pc is 0.5 to 1 the expected aggregate structure is vesicle bilayer
structure.
* So formed bilayer vesicle mimic biological cell membrane and have
similar interactions which help in adsorption of vesicles on the cell
membranes.

9. Role of cholesterol
• Cholesterol, a natural steroid, is the
most commonly used membrane
additive
• Stabilize the system against the
formation of aggregates by repulsive
steric or electrostatic effects
• Prevents the transition from the gel
state to liquid phase in niosomes
systems by increasing hydrophobic
interactions.
• Niosomes become less leaky as
cholesterol seals the pores or spaces on
the bilayer.
Cholesterol

10. Small
Unilamellar
Vesicle
(SUV)
Large
Unilamellar
Vesicle
(LUV)
Multilamellar
vesicles(MLV)
Typical Size Ranges: ULV: 20-50 nm – MLV:100-1000 nm

11. Advantages of niosomes
• They possess an infrastructure consisting of hydrophobic and
hydrophilic moieties together and as a result can accommodate
drug molecules with a wide range of solubilities
• They improve the therapeutic performance of the drug
molecules by delaying the clearance from the circulation,
protecting the drug from biological environment, and
restricting effects to target cells
• Handling and storage of surfactants requires no special
conditions.

12. • Enhance skin penetration of drugs
.
• The vesicle suspension being water based offers greater
patient compliance over oil based systems
• Act as a depot to release drug slowly
• The surfactants are biodegradable, biocompatible, and non
immunogenic.

13. Advantages of niosomes over
liposomes
o In case of liposomes ,Ester bonds of phospholipids are easily
hydrolyzed, at low pH
o Peroxidation of unsaturated phospholipids.
oAs liposomes have purified phospholipids they are to be
stored and handled at inert(N2) atmospheres where as
Niosomes are are made of non ionic surfactants and are
easy to handle and store.
oPhospholipid raw materials are naturally occurring
substances and as such require extensive purification thus
making them costly

14. Mechanism of Niosome
1.Acts as Permeation enhancer In Topical
preparation : Increases penetration of drug
by destabilizing the stratum corneum.
2.Acts as targeting agent : drug targeting
includes both passive targeting and active
targeting.
•Passive targeting seen incase of solid tumors.
• Active targeting includes : Ligand mediated
targeting and physical mediated targeting (pH
or temp changes)

15. Stealth niosomes
• Any foreign matter is recognized by human immune system i.e,
macrophages engulf them and provide protection.
• Opsonins are proteins which help macrophages in engulfing the foreign
matter ( including niosomes) .
• Opsonins attach on niosomes and helps macrophages to recognize the
niosomes for phagocytosis, Which result in degradation of niosomal
preparation.
• Stealth niosomes are one which prevent the attachment of opsonins on
it.
• Stealth niosomes are prepared by coating the niosomes with
hydrophillic and non ionic polymers for ex PEG and its derivatives.

16. • Absence of electrostatic and hydrophobic forces and also steric
hindrance of PEG opsonins cannot bind to niosomes.
• PEG have flexible and extended conformation which prevents
the opsonins in binding to the niosomes by creating strong
repulsive forces.

17. Formulation of niosomes
1.Ether injection method.
It is essentially based on slow injection of surfactant : cholesterol in
ether (20ml) through a 14 gauge needle at approximately 0.25
ml/min. into a pre-heated aqueous phase maintained at 60°C.
Vaporization of ether leads to formation of single layered vesicles.
Later it results in the formation of a bilayer sheet, which eventually
folds on itself to form sealed vesicles.
 Depending upon the conditions used, the diameter of the vesicle
range from 50 to 1000 nm.

18. 2.. Hand shaking method (Thin film hydration technique).
The mixture of vesicles forming ingredients like surfactant and
cholesterol are dissolved in 10 ml of volatile organic solvent (diethyl
ether, chloroform or methanol) in a round bottom flask.
 The organic solvent is removed at room temperature (20°C) using
rotary evaporator leaving a thin layer of solid mixture deposited on the
wall of the flask.
 The dried surfactant film can be rehydrated with aqueous phase by
gentle agitation.
 This process forms typical multilamellar niosomes. The liquid volume
entrapped in vesicles appears to be small, i.e. 5-10%.

19. 3. Sonication.
 A typical method of production of the vesicles is by sonication of
solution.
In this method an aliquot of drug solution in buffer is added to the
surfactant/cholesterol mixture in a 10-ml glass vial.
 The mixture is probe sonicated at 60°C for 3 minutes using a
sonicator with a titanium probe to yield niosomes.
The method involves the formation of MLVs which are
subjected to ultrasonic vibrations.
Probe sonicator - when the volume of sample is small.
Bath sonicator - when the volume of sample is large.
Vesicles obtained are unilamellar in shape .
*Care must be taken while working with temperature sensitive
solute.

20. 4.The “Bubble” Method.
 It is novel technique for the one step preparation of liposome and
niosomes without the use of organic solvents.
The bubbling unit consists of round-bottomed flask with three necks
positioned in water bath to control the temperature.
 Water-cooled reflux and thermometer is positioned in the first and
second neck and nitrogen supply through the third neck.
Cholesterol and surfactant are dispersed together in this buffer (pH 7.4)
at 70°C, the dispersion mixed for 15 seconds with high shear
homogenizer and immediately afterwards “bubbled” at 70°C using
nitrogen gas

21. 5.Reverse Phase Evaporation Technique (REV)
LUVs can also be prepared by forming a water in oil
emulsion of surfactants and buffer in excess organic
phase followed by removal of the organic phase under
reduced pressure ( so called reverse phase
evaporation)
 The two phases are usually emulsified by sonication
 The lipid or surfactant forms a gel first and
subsequently hydrates to form vesicles. Free drug
(unentrapped) is generally removed by dialysis.

22. Dialysis
Separation of
unentrapped
material from
niosomes
Gel filtration Centrifugation
Filtration

23. Separation of Unentrapped Drug
1. Dialysis
The aqueous niosomal dispersion is dialyzed in a dialysis tubing against
phosphate buffer or normal saline or glucose solution.
2. Gel Filtration
The unentrapped drug is removed by gel filtration of niosomal dispersion
through a Sephadex-G-50 column and elution with phosphate buffered
saline or normal saline.
3. Centrifugation
The niosomal suspension is centrifuged and the supernatant is separated.
The pellet is washed and then resuspended to obtain a niosomal
suspension free from unentrapped drug.

24. Characterization
1.Entrapment efficiency
After preparing niosomal dispersion, unentrapped drug is separated by
dialysis and the drug remained entrapped in niosomes is determined by
complete vesicle disruption using 50% n-propanol or water soluble
marker 0.1% Triton X-100 and analysing the resultant solution by
appropriate assay method for the drug.
2.Size, Shape and Morphology :
Electron Microscopy and light scattering :- Morphological studies of
vesicles
Gel chromatography : size distribution

25. 3.Niosomal drugloading and encapsulation efficiency
The niosomal aqueous suspension was ultracentrifuged,supernant was
removed and sediment was washed twice with distilled water in order to
remove the adsorbed drug.
Amount of drug in niosomes
Entrapment efficiency (%)= --------------------------------------------X 100
Amount of Drug used
4. Vesicle Suface Charge
Determined by measurement of electrophoretic mobility and expressed
in terms of zeta potential

26. 5. Niosomal drug release
The simplest method to determine invitro release kinetics of the
loaded drug is by incubating a known quantity of drug loaded
niosomes in a buffer of suitable pH at 37°c with continuous stirring
,withdrawing samples periodically and analysed the amount of
drug by suitable analytical technique.dialysis bags or dialysis
membranes are commonly used to minimize interference.

27. Evaluation of Niosomes
In-vitro release :
 A method of in-vitro release rate study includes the use of
dialysis tubing.
 A dialysis sac is washed and soaked in distilled water. The vesicle
suspension is pipetted into a bag made up of the tubing and
sealed.
 The bag containing the vesicles is placed in 200 ml of buffer
solution in a 250 ml beaker with constant shaking at 25°C or 37°C.
 At various time intervals, the buffer is analyzed for the drug
content by an appropriate assay method of vesicles during the
cycle.

28. Franz diffusion cell:
• In a Franz diffusion cell, the cellophane membrane is
used as the dialysis membrane.
• The niosomes are dialyzed through a cellophane
membrane against suitable dissolution medium at room
temperature.
• The samples are withdrawn at suitable time intervals
and analyzed for drug content.

29. Limitations
• Aggregation on storage may be the drawback for the
niosome preparation .
• To avoid this instability Proniosomes are discovered.
Proniosomes are dry formulation of surfactant coated
carrier, which can be measured out as needed and
rehydrated by brief agitation in hot water.
Advantages:
• Convenience of storage, transport and dosing.
• More stable formulations.
• Being dry powders makes processing and packaging easier.

30. Method of formation
To create proniosomes, a water soluble carrier such as sorbitol is
first coated with the surfactant. The coating is done by preparing a
solution of the surfactant with cholesterol in a volatile organic
solvent, which is sprayed onto the powder of sorbitol kept in a
rotary evaporator.
 The evaporation of the organic solvent yields a thin coat on the
sorbitol particles. The resulting coating is a dry formulation in
which a water soluble particle is coated with a thin film of dry
surfactant. This preparation is termed Proniosome.
The niosomes can be prepared from the proniosomes by adding
the aqueous phase with the drug to the proniosomes with brief
agitation at a temperature greater than the mean transition phase
temperature of the surfactant.

32. THERAPEUTIC APPLICATIONS
TREATMENT OF NEOPLASIA
The anthracyclic antibiotic Doxorubicin, with broad
spectrum anti tumour activity, shows a dose dependent
irreversible cardio toxic effect.
The halflife of drug increased by its niosomal entrapment of the drug and
also prolonged its circulation and its metabolisom altered
If the mice bearing S-180 tumour is treated with niosomal
delivery of this drug it was observed that their life span
increased and the rate of proliferation of sarcoma
decreased.
Methotrexate entrapped in niosomes if administered
intravenously to S-180 tumour bearing mice results in total
regression of tumour and also higher plasma level and
slower elimination.

33. • Treatment of mitochondrial disorders :
Drug should released intracellular and should be protected from
lysosomal degradation. In this case niosomal preparation of
medication (ubiquinone,ubiquinol) by using DOPE-PEG as coating
material which prevents lysosomal degradation of the preparation.

34. • Treatment of vitiligo :
Topical application of corticosteroids and calcium modulators using
niosomal preparation.
Niosomes known to enhance the permeation and facilitate the drug
transport across the skin.
• Treatment of glaucoma :
Ophthalmic preparations of a acetazolamide niosomal preparation
results in Increased corneal permeability and increases drug delivery.

35. Leishmaniasis therapy
• Derivatives of antimony are most commonly prescribed
drugs for the treatment of leishmaniasis.
• These drugs in higher concentrations – can cause liver,
cardiac and kidney damage.
• Use of niosomes as a drug carrier showed that it is
possible to overcome the side effects at higher
concentration also and thus showed greater efficacy in
Treatment.

36. • Magnetic Niosomes acts as contrasting agent in MRI imaging.
• Niosomes as immunological adjuvant

37. List of Drugs formulated as Niosomes
Intravenous route Doxorubicin, Methotrexate, Sodium Stibogluconate, Vincristine,
Flurbiprofen, , Indomethacin, Colchicine,Rifampicin, Tretinoin,
Transferrin and Glucose ligands, Zidovudine, Insulin,Cisplatin, Amarogentin,
Daunorubicin, Amphotericin B, 5-Fluorouracil, Camptothecin
Transdermal route Flurbiprofen, Piroxicam, Estradiol
Levonorgestrol,Nimesulide,Dithranol, Ketoconazole, Enoxacin, Ketorolac
Ocular route Timolol Maleate, Cyclopentolate
Nasal route Sumatriptan, Influenza Viral Vaccine
Inhalation All - trans retinoic acids

38. Marketed formulations
• Lancome has come out with a variety of anti-ageing products
which are based on niosome formulations .
Anti ageing cream consists of D-Contraxol it is said to reduce the
depth of wrinkles by working on the neuro -transmitters
responsible for muscle contraction

39. PHARMACOSOMES

40. INTRODUCTION:
• Pharmacosomes are the colloidal dispersions of drugs covalently
bound to lipids, and may exist as ultrafine vesicular, micellar, or
hexagonal aggregates, depending on the chemical structure of
drug-lipid complex.
• Pharmacosomes are amphiphilic phospholipid complexes of drugs
bearing active hydrogen that bind to phospholipids.
• Pharmacosomes impart better biopharmaceutical properties to
the drug, resulting in improved bioavailability.

41. • Pharmacosomes have been prepared for various non-steroidal anti-inflammatory
drugs, proteins, cardiovascular and antineoplastic drugs.
• Developing the pharmacosomes of the drugs has been found to
improve the absorption and minimize the gastrointestinal toxicity.

42. IMPORTANCE:
• Pharmacosomes have importance in escaping the tedious steps of
removing the free unentrapped drug from the formulation.
• Pharmacosomes provide an efficient method for delivery of drug
directly to the site of infection, leading to reduction of drug toxicity
with no adverse effects and also reduces the cost of therapy by
improved bioavailability of medication, especially in case of poorly
soluble drugs.
• Pharmacosomes are suitable for incorporating both hydrophilic and
lipophilic drugs.
• Entrapment efficiency is not only high but predetermined, because
drug itself in conjugation with lipids forms vesicles

43. • There is no need of following the tedious, time-consuming step for
removing the free, unentrapped drug from the formulation.
• Since the drug is covalently linked, loss due to leakage of drug, does
not take place.
• No problem of drug incorporation
• Encaptured volume and drug-bilayer interactions do not influence
entrapment efficiency, in case of pharmacosomes

44. • In pharmacosomes, membrane fluidity depends upon the phase
transition temperature of the drug lipid complex, but it does not affect
release rate since the drug is covalently bound.
• The drug is released from pharmacosome by hydrolysis (including
enzymatic).
• The physicochemical stability of the pharmacosome depends upon the
physicochemical properties of the drug-lipid complex.
• Following absorption, their conversion into active drug molecule
depends to a great extent on the size and functional groups of drug
molecule, the chain length of the lipids, and the spacer.

45. PREPARATION:
• Two methods have been used to prepare vesicles:
1. The hand-shaking method
2. The ether-injection method
• In the hand-shaking method, the dried film of the drug–lipid complex is
deposited in a round-bottom flask and upon hydration with aqueous
medium, readily gives a vesicular suspension.
• In the ether-injection method, an organic solution of the drug–lipid
complex is injected slowly into the hot aqueous medium, wherein the
vesicles are readily formed.

46. FORMULATION OF PHARMACOSOMES:
• Drug salt was converted into the acid form to provide an active
hydrogen site for complexation.
• Drug acid was prepared by acidification of an aqueous solution of
drug salt, extraction into chloroform, and subsequent
recrystallization.
• Drug -PC complex was prepared by associating drug acid with an
equimolar concentration of PC.

47. • The equimolar concentration of PC and drug acid were placed in a
100-mL round bottom flask and dissolved in dichloromethane.
• The solvent was evaporated under vacuum at 40°C in a rotary
vacuum evaporator.
• The pharmacosomes were collected as the dried residue and
placed in a vacuum desiccator overnight and then subjected to
characterization.

48. EVALUATION OF PHARMACOSOMES:
• Solubility
• Drug content
• Differential scanning calorimetry
• X-ray powder diffraction (XRPD)

49. Solubility:
• To determine the change in solubility due to complexation, solubility
of drug acid and drug-PC complex was determined in pH 6.8
phosphate buffer and n-octanol by the shake-flask method.
• Drug acid (50 mg) (and 50 mg equivalent in case of complex) was
placed in a 100-mL conical flask. Phosphate buffer pH 6.8 (50 mL) was
added and then stirred for 15 minutes.
• The suspension was then transferred to a 250 mL separating funnel
with 50 mL n-octanol and was shaken well for 30 minutes.
• Then the separating funnel was kept still for about 30 minutes.
Concentration of the drug was determined from the aqueous layer
spectrophotometrically at 276 nm.

50. Drug content:
• To determine the drug content in pharmacosomes of drug (e.g.:
diclofenac-PC complex), a complex equivalent to 50 mg diclofenac
was weighed and added into a volumetric flask with 100 mL of pH 6.8
phosphate buffer.
• Then the volumetric flask was stirred continuously for 24 h on a
magnetic stirrer. At the end of 24 h, suitable dilutions were made and
measured for the drug content at 276 nm UV spectrophotometrically.

51. Differential scanning calorimetry
(DSC):
• Thermograms of drug acid, phosphatidylcholine (80 %) and the drug
-PC complex were recorded using a 2910 Modulated Differential
Scanning Calorimeter V4.4E (TA Instruments, USA).
• The thermal behavior was studied by heating 2.0 ± 0.2 mg of each
individual sample in a covered sample pan under nitrogen gas flow.
The investigations were carried out over the temperature range 25–
250 °C at a heating rate of 10 °C min–1.

52. X-ray powder diffraction (XRPD):
• The crystalline state of drug in the different samples was
evaluated using X-ray powder diffraction. Diffraction patterns
were obtained on a Bruker Axs- D8 Discover Powder X-ray
diffractometer, Germany.
• The X-ray generator was operated at 40 kV tube voltages and 40
mA tube current, using lines of copper as the radiation source.
The scanning angle ranged from 1 to 60° of 2q in the step scan
mode (step width 0.4° min–1).
• Drug acid, phosphatidylcholine 80 % (Lipoid S-80) and the
prepared complex were analyzed.

53. APPLICATIONS:
• The approach has successfully improved the therapeutic
performance of various drugs i.e. pindolol maleate, bupranolol
hydrochloride, taxol, acyclovir, etc.
• The phase transition temperature of pharmacosomes in the
vesicular and Micellar state could have significant influence on
their interaction with membranes.
• Pharmacosomes can interact with biomembranes enabling a
better transfer of active ingredient. This interaction leads to
change in phase transition temperature of biomembranes thereby
improving the membrane fluidity leading to enhance
permeations.

54. Conclusion
• The concept of incorporating the drug into niosomes for a better
targeting of the drug at appropriate tissue destination .
• They presents a structure similar to liposome and hence they can
represent alternative vesicular systems with respect to liposomes
• Niosomes are thoughts to be better candidates drug delivery as
compared to liposomes due to various factors like cost, stability etc.
Various type of drug deliveries can be possible using niosomes like
targeting, ophthalmic, topical, parentral, etc.

55. • Vesicular systems have been realized as extremely useful carrier
systems in various scientific domains. Over the years, vesicular
systems have been investigated as a major drug delivery system,
due to their flexibility to be tailored for varied desirable purposes.
• In spite of certain drawbacks, the vesicular delivery systems still play
an important role in the selective targeting, and the controlled
delivery of various drugs.
• Researchers all over the world continue to put in their efforts in
improving the vesicular system by making them steady in nature, in
order to prevent leaching of contents, oxidation, and their uptake by
natural defense mechanisms.

56. References:
• S.P. Vyas R.K.Khar, Targeted And Controlled Drug Delivery novel carrier
systems ; niosomes (p no.249-276)
• N.K.JAIN , Controlled and Novel Drug Delivery; niosomes
p no.(292-301)
• H.A. Lieberman, M.M. Rieger, and G.S. Banker,
Pharmaceutical Dosage Forms: Disperse Systems p. 163.
• International Journal of Biopharmaceutics.2011;2(1):47-53; NIOSOMES
FORMULATION AND EVALUATION

57. • Review article of PHARMACOSOMES: A Potential vesicular drug delivery
system BY de pintu kumar,de arnab
• Review article of PHARMACOSOMES:opening new doors for drug delivery
BY anu goyal