AQUASOME IS SELF ASSEMBLED 3 LAYER NANO PARTICLUATE DRUG DELIVERY SYSTEMS

1. A SEMINAR ON
AQUASOME
PRESENTED BY
SOUMYADIP GHOSH
M.PHARM, PHARMACEUTICS , 2ND sem
ROLLNO - 15920320002
DEPARTMENT OF PHARMACEUTICS
CALCUTTA INSTITUTE OF PHARAMCEUTICAL TECHNOLOGY AND AHS
ULUBERIA , WEST BENGAL

2. CONTENT OFAQUASOME
 INTRODUCTION
 PROPERTIES
 PRINCIPLE OF SELF ASSEBLY
 METHOD OF PREPARATION
 EVALUATION
 ADVANTAGES
 APPLICATIONS
 CONCULSION
 REFERENCES

3. INTRODUCTION
 AQUASOME are the nanoparticulate carrier systems BUT instead of being simple nanoparticle
these are three layered self assembeled structure comprised of a solid phase nanocrystalline
core coated with oligomeric film to which biochemically active molecules are adsorbed with or
without modification .
 Aquasomes are spherical 60-300nm particles used for drug and antigen delivery.
 It was first developed by NIR KOSSOVSKY.

4. AQUASOMES are called as “ bodies of water ’’
1 Their water like properties.
2 Protect and preserve fragile biological molecules.
3 This property of maintaining conformational integrity as well as high degree
of surface exposure and in targeting of bio-active molecules like peptide and
protein hormones, antigens and genes to specific sites.
The carbohydrate stabilize nanoparticle of ceramic are known as “AQUASOMES”

5. PROPERTIES OF AQUASOME
1) Aquasomes water like properties provides a platform for preserving the
conformational Integrity and bio chemical stability of bio-actives.
2) Aquasomes due to their size and structure stability, avoid clearance by
reticuloendothelial system or degradation by other environmental
challenges.
3) Aquasomes possess large size and active surface hence can be efficiently
loaded with substantial amounts of agents through ionic, non covalent
bonds, van der waals forces and entropic forces. As solid particles
dispersed in aqueous environment, they exhibit physical properties of
colloids.

6. 4) In general these aquasomes are assemblies of simple polymers,
complex lipid mixtures with diameter ranging between 60 to 300
nm.
5) As these are solid or glassy particles dispersed in an aqueous
environment, they exhibit the physical properties of colloids and
their mechanism of action is controlled by their surface chemistry.
6) Aquasome delivers the content through the combination of specific
targeting , slow and sustain release process .
CONTINUE

7. PRINCIPLE OF SELF ASSEMBLY
In aqueous biological environment , the assembly
of macromolecular governed by three process ,
1) Interaction between charged group.
2) Hydrogen bonding and dehydration effect.
3) Structural stability.

8. 1 ) INTERACTION BETWEEN CHARGED GROUP
 Most of the Biological product are charged due to intrinsic
chemical group or absorbed ion from the biological
environment.
 Interaction of charged group such as amino, carbonyl,
sulphate, phosphate groups facilitate the long range
approach of self assembling sub units.
 Charged groups also play role in stabilizing tertiary structure
of folded proteins.
 Example of ion pairs -carboxylated /phosphate group bound
to ionized arginine /lysine side chain of protein.

9. 2) HYDROGEN BONDING AND DEGYDRATION EFFECT
Hydrogen bond are formed between hydrogen atom
attached to an electronegative donor atom (Ex. oxygen,
Nitrogen) and an electronegative or basic acceptor (Ex .
carbonyl oxygen).
Hydrogen bond help in base pair matching and stabilization
of Secondary protein structure.
Molecule that form hydrogen bonds are hydrophilic and
these molecules confers significant degree of organization to
the surrounding water molecules.

10. 3) STRUCTURAL STABILITY
The structural stability of Protein in the biological
environment is determined by the interaction between charged
groups and hydrogen bond largely external to the molecule
and vander walls forces largely internal to the molecule.
VANDER WALLS FORCES are largely responsible for the
hardness or softness of the molecule. The vander walls
interaction among hydrophilic side chains promotes stability of
compact helical structures.

11. METHOD OF PREPARATION
 By using the principle of self assembly Aquasomes can be prepared by three method,
1) Formation of an inorganic core
2) Coating of the core with poly hydroxy oligomer .
3) Loading of the drug of choice of the assembly.

12. 1) FORMATION OF AN INORGANIC CORE
 This stage mainly depends on the selection of material for core,
-its physical chemical properties.
 This can be fabricated by the,
-Sonication
-Colloidal precipitation
 For the core material material ceramic material widely used ,as
they are structurally to be known

13. CONTINUE
 Commonly used ceramic core are tin oxide,and calcium
phosphate.
EXAMPLE - Synthesis of nano crystalline tin
oxide core material
 This can be prepared by
A.Direct current reactive
B.Magnetron sputtering

14. 3 Inch diameter target of highly purified Tin is sputterd in
High pressure gas mixture of argon and oxygen.
The ultra fine particle form in gas phase are collect on copper
tube and cool at 700K with liquid nitrogen
SYNTHESIS OF NANO CRYSTALLINE TIN OXIDE
CORE MATERIAL

15. SYNTHESIS OF NANO CRYSTALBRUSHITE (CALCIUMPHOSPHATE
DIHYDRATE)
 This can be prepared by
-colloidal dispersion
-Sonication
-By reaction of di-sodium hydrogen phosphate and calcium
phosphate or calcium chloride (cacl2).
 The commonly feature include
 Crystalline
 The measure between 50-150nm and exhibit clean and reactive
surface area .

16. 2) Coating of the core with poly hydroxy oligomer
The second step involves coating by carbohydrate on
the surface of ceramic cores.
There are number of processes to enable the
carbohydrate (polyhydroxy oligomers) coating to
adsorb epitaxially on to the surface of the Nano
crystalline ceramic cores.

17. Addition of poly hydroxy oligomer
To a dispersion of core in ultra purewater
Lyophilization (to promote the adsorption of carbohydrate on the surface of
ceramiccore)
Excess of carbohydrate is removed by stir cell ultrafilteration
• Generally used coating materials are cellobiose , citrate , pyridoxil
5 phosphate and sucrose .
Process generally entail,

18. 3) Loading of the drug of choice of the assembly
 The final stage includes the loading of drug to the coated particles by
adsoption .
Solution of the known concentration in pH buffer
coated particles are dispersed into it
Dispersion is kept over night or lyophilized
AQUASOME

19. EVALUATION

20. CHARACTERIZATION OF CERAMIC CORE
Size distribution:
 For morphological charecterization and size distribution analysis
, Scanning electrone microscopy(SEM) , Transmission electron
microscopy (TEM) are generally used .
Mean particle size and zeta potential of the particles can also be
determined by using photon correlation spectroscopy

21. STRUCTURALANALYSIS:
FT-IR spectroscopy can be used for structural analysis. Using the
potassium bromide sample disk method, the core as well as the
coated core can be analyzed by recording their IR spectra in the wave
number range 4000-400 cm -1;
CRYSTALLINITY:
 The prepared ceramic core can be analyzed for its crystalline or amorphous
behavior using X-ray diffraction. In this technique, the X-ray diffraction
pattern of the sample is compared with the standard diffractogram, based on
which the interpretations are made.

22. CHARECTERIZATION OF COATED CORE
CARBOHYDRATE COATING
Coating of sugar over the ceramic core can be confirmedby
1) CONCANAVALIN A- Induced aggregation method (determines
the amount of sugar coated over core)
2) ANTHRONE METHOD – Determines the residual sugar
unbound or residual sugar remaining after coating .
3) Furthermore, the adsorption of sugar over the core can also be
confirmed by measurement of zeta potential.

23. CHARACTERIZATION OF DRUG-LOADED AQUASOME
DRUG PAYLOAD
 The drug loading can be determined by measuring the drug remaining in the supernatant
liquid after loading which can be estimated by any suitable method of analysis.
IN VITRO DRUG RELEASE STUDIES
1) The in vitro release kinetics of the loaded drug is determined to study the release pattern of
drug from the aquasomes by incubating a known quantity of drug-loaded aquasomes in a
buffer of suitable pH at 37°C with continuous stirring.
2) Samples are withdrawn periodically and centrifuged at high speed for certain lengths of
time. Equal volumes of medium must be replaced after each withdrawal. The supernatants
are then analyzed for the amount of drug released by any suitable method .

24. ADVANTAGES
1. Aquasome conserves the structural veracity and biochemical constancy of drug
particles .
2. Due to their specific size and structural stability , aquasomes evade RES
(Reticuloendothelial clearance) or degradation in acidic pH or so forth.
3. Aquasomes displays colloidal characteristics .
4. Aquasome suspension contains colloidal range biodegradable nanoparticles , chance
of accumulation in muscles and liver is high .
5. Receptor recognition is not difficult as the drug is easily adsorbed on the surface of
aquasome , hence site – specific delivery of biomolecules can be achieved easily .
6. Aquasome own large size and an active surface hence , substantial amount of drug
molecules can be surface adsorbed through ionic , non – covalent bonds , van der walls
forces and entropic forces .
7. Drug release from aquasomes can be controlled by altering their surface through
combination of specific targeting , molecular shielding, and controlled release of
therapeutics .

25. APPLICATION OF AQUASOME
 Aquasomes has got a quite versatile application potential as a carrier
for delivery of vaccines, hemoglobin, drugs, dyes, enzymes ,
1) Aquasomes used as vaccines for delivery of viral antigen
2) Aquasomes as red blood cell substitutes can effectively deliver the
large, complex labile molecule, haemoglobin by incorporating in
aquasome carriers, the toxicity of haemoglobin is reduced,
biological activity is preserved, haemoglobin concentration of 80%
can be achieved and is reported to deliver oxygen in a non linear
manner like natural red blood cells.

26. 3) Aquasomes for pharmaceuticals delivery i.e. insulin, developed
because drug activity is conformationally specific. Bio activity
preserved and activity increased to 60% as compared to i.v.
administration and toxicity not reported .
4)Aquasomes are used for oral delivery of acid labile enzyme,
serratiopeptidase. Enzyme loaded aquasome was further protected by
encapsulating in alginategel.
 They protected structural integrity of enzymes and better
therapeutic efficacy was observed
CONTINUE

27. CONCLUSION
AQUASOME, the self-assembling surface- modified nanocrystalline
ceramic cores , seem to have potential and promising carriers capable
of preserving the structural integrity of protein pharmaceuticals and
carrier for delivery of broad range of molecules including viral
antigen , heamoglobin and insulin , thus promoting a better
therapeutic effect.
Also these formulation gave been to evoke a better
immunological response and could be use as immunoadjuvants for
proteinaceous antigen .This approach thus provides pharmaceutical
scientists with new hope for the delivery of bioactive molecules .

28. REFERENCE
1)Sanjay s. jain , Pramod s. et al ,Aquasome- a novel drug carrier, journal of
applied pharmaceutical science 02(01);2012:184-192
2)Vyas S.P and khar R.K, Controlled Drug Delivery- concepts and advances ,
Ballabh Prakashan , New Delhi (2004) 28-30
3)Jain NK. Advances in controlled and novel drug delivery systems. CBS
publishers and Distributor, New Delhi(2001)317-328
4)Jain NK, Ummamaheshwari RB. Controlled and novel drug delivery
systems. In: Jain NK, editor. Pharmaceutical product development. CBS
Publishers & Distributors, New Delhi (2006)419-455
5)Vyas S.p., Goyal A.K., Khatri K, Mishra N.,Mehta A ., Vaifya, B., et al.
Aquasome- a nanoparticulate approach for the delivery of antigen. Drug
development Ind Pharm. 2006;309:227-233

29. THANK YOU FOR PATIENT
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