Basic Overview of Aquasome Technology

1. AQUASOMES
Presented By:-
Minakshi Rathee
Dept. of Pharmaceutical Sciences
PDM University

2. Contents
• Introduction
• Objective
• Properties of Aquasomes
• Principle of Self Assembly
• Method of Preparation of
Aquasomes
• Characterization
• Application
• Conclusion

3. Introduction
• Aquasomes were first
discovered by Nir Kossovsky.
• These are nanoparticulate
carrier system with three
layered self assembled
structures.
• These comprises of central
solid nanocrystalline core
coated with polyhydroxy
oligomers onto which
biochemically active molecules
are adsorbed.

4. • Aquasomes are also called as “Bodies of Water”, and their
water like properties protect and preserve fragile biological
molecules.
• maintain conformational integrity as well as high degree of
surface exposure .
• The carbohydrates stabilize nanoparticle of ceramic are
known as “Aquasomes”.
• Aquasomes are spherical 60-300nm particles used for drug
and antigen delivery.

5. Objective
• The main objective of preparing aquasomes is to
protect bio-actives.
• aquasomes carbohydrate coating prevents
destruction denaturing interaction between drug and
solid carriers.
• Aquasomes maintain molecular confirmation and
optimum pharmacological activity.

6. Properties
of
Aquasomes
Provides a platform for preserving the
conformational integrity of bioactive
substances.
Deliver their contents through a
combination of specific targeting, slow and
sustained release.
Calcium phosphate is biodegradable in
nature and its degradation can be achieved
by monocytes and osteoclasts.
Protects the drug/antigen/protein from
harsh pH conditions & enzymatic
degradation.
They exhibit the physical properties of
colloids & their MOA is controlled by their
surface chemistry.

7. Principle of Self Assembly
Governed by 3 Processes
Interaction Between Charged Particles
Hydrogen Bonding & Dehydration Effect
Structural Stability
A
B
C

8. Method of Preparation of Aquasomes
Preparation of Core
Coating of Core
Immobilization of Drug Molecule
1
2
3

9. 1) Preparation of Core
• It mainly depends upon-
• Selection of material for core
• Its physical chemical properties
• This can be fabricated by-
• Sonication
• Colloidal precipitation
• For the core material, ceramic material is widely used as they are
structurally to be known.
• Commonly used ceramic core tin oxide and calcium phosphate.

10. Example:- Synthesis of nanocrystalline tin
oxide core material.
This can be prepared by Direct current reactive:
a
• 3 inch diameter target of highly purified tin is sputtered in
b
• High pressure gas mixture of argon and oxygen.
c
• The ultrafine particles form in gas phase are collected on
copper tube and cooled to 70°K with liquid nitrogen.

11. 2) Coating of Core
• The second step involves the coating by carbohydrate
on the surface of ceramic cores.
• There are number of processes to enable the
carbohydrate(polyhydroxy oligomers) coating to
absorb epitaxially on to the surface or the nano
crystalline ceramic cores.
• Commonly used coating materials are-
• Cellobiose, Citrate, Sucrose, Trihalose.

12. Process generally entails
Addition of polyhydroxy oligomer
To a dispersion of core in ultra pure water
Lyophilization (to promote the adsorption of
carbohydrate on the surface of ceramic core)
Excess of carbohydrate is removed by stir cell
ultrafiltration.

13. 3) Immobilization of Drug
• The surface modified nano crystalline core provide the solid phase for
subsequent non denaturing self assembly for a broad range of biological
active molecule.
• Drug can be loaded by partial adsorption.

14. Characterization of Ceramic Core
Size Distribution
• For morphological
characterization and size
distribution analysis.
• SEM, TEM, are generally
used.
• Mean particle size and zeta
potential of the particles can
also be determined by using
photo correlation
spectroscopy.
Structural Analysis
• FT-IR Spectroscopy.
• Crystallinity
• The prepared ceramic
core can be analyzed for
its crystalline or
amorphous behavior
using X-Ray Diffraction.

15. Characterization of Coated Core
• Carbohydrate Coating
• Coating of sugar over the ceramic core can be confirmed
by
i. Concanavalin-A induced aggregation method :- Determines
the amount of sugar coated over core, or
ii. Anthrone method:- Determines the residual sugar
unbound or residual sugar remaining after coating.
iii. Furthermore, the adsorption of sugar over the core can
also be confirmed by measurement of zeta potential.

16. Characterization of Drug loaded
Aquasomes
• 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
• 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.
• 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.

17. Applications of Aquasomes
• As oxygen carrier
• Antigen delivery
• Insulin delivery
• Gene therapy
• Delivery of enzymes
• Delivery of drug
• For vaccine

18. As oxygen carrier
• Patil and co-workers prepared hydroxyapatite ceramic cores by co-precipitation
and self-precipitation.
• Hemoglobin was adsorbed over the coated ceramic core, and the percentage
drug loading was estimated by the benzidine method.
• The oxygen carrying capacity of aquasome formulation was found to be similar
to that of fresh blood.
• Also, the Hill coefficients were found to be good for its use as an oxygen carrier.
• The aquasome formulations neither induced hemolysis of the red blood cells
nor altered the blood coagulation time.
• No significant increase in arterial blood pressure and heart rate was observed in
rats transfused with aquasome suspension on 50% exchange transfusion.

19. Antigen delivery
• With the help of aquasomes a strong and specific immune response
could be elicited by enhancing the availability and in vivo activity of
antigen.
• Aquasomes are prepared by self-assembling of hydroxyapatite using
the co-precipitation method.
• The core was coated with cellobiose and trehalose, and finally bovine
serum albumin was adsorbed as model antigen onto the coated core.
• The aquasomes were found to be spherical in shape with diameter
around 200 nm.
• The antigen-loading efficiency was found to be approximately 20–
30%.

20. Insulin delivery
• Aquasomes are prepared using a calcium phosphate ceramic
core for the parenteral delivery of insulin.
• The core was coated with various disaccharides such as
cellobiose, trehalose, and pyridoxal-5-phosphate.
• Subsequently the drug was loaded to these particles by
adsorption method.
• Pyridoxal-5-phosphate coated particles were found to be more
effective in reducing blood glucose levels than aquasomes
coated with trehalose or cellobiose.
• Porous hydroxyapatite nanoparticles entrapped in alginate
matrix containing insulin for oral administration.

21. Aquasomes
for Insulin
Delivery
a)
Na2HPO4 and CaCl2
b)
Prepare calcium phosphate dihydrate
core.
c)
Core further coated with coating
material like cellobiose citrate,
pyridoxal-5-phosphate under sonication
d)
Drug is loaded to these coated nano
particle/ Aquasomes.

22. Gene therapy
• Aquasomes delivery system loaded with genetic material.
• Aquasomes protect and maintain structural integrity of the
gene segment.
• A five layered composition comprised of the ceramic
nanocrystalline core, the polyhydroxyl oligomeric film
coating, the non covalently bound layer of therapeutic gene
segment, an additional carbohydrate film and a targeting layer
of conformationally conserved viral membrane proteins, have
been proposed for gene therapy.

23. •

24. Delivery of enzymes
• The use of a nanosized ceramic core–based system for oral administration
of the acid-labile enzyme serratiopeptidase.
• The nanocore was prepared by colloidal precipitation under sonication at
room temperature.
• The core was then coated with chitosan under constant stirring, after which
the enzyme was adsorbed over it.
• The enzyme was protected by further encapsulating the enzyme-loaded
core into alginate gel.
• The TEM images of particles showed them to be spherical in shape, with
an average diameter of 925 nm.
• The enzyme-loading efficiency of the particles was found to be
approximately 46%.

25. Delivery of drug
• Aquasomes loaded with indomethacin through the
formation of an inorganic core of calcium
phosphate covered with a lactose film and further
adsorption of indomethacin as a low-solubility drug.
• Particle size of drug-loaded aquasomes was found to
be in the range of 60–120 nm.
• SEM and TEM techniques confirmed the spherical
shape of aquasomes.

26. For vaccine
• An adjuvant and delivery vehicle for hepatitis B vaccine for
effective immunization.
• Self-assembling hydroxyapatite core was coated with cellobiose,
and finally hepatitis B surface antigen was adsorbed over the
coated core.
• The drug-loaded particles were in the nanometer range and
almost spherical in shape.
• The antigen-loading efficiency of plain hydroxyapatite core
(without cellobiose coating) was found to be approximately
50%, whereas the coated core was observed to load
approximately 21% antigen

27. Conclusion
• Aquasomes represent one of the simplest yet a
novel drug carrier based on the fundamental
principle of self assembly. The drug candidates
delivered through the Aquasomes show better
biological activity even in case of conformationally
sensitive ones.
• In conclusion, aquasomes appear to be promising
carriers for the delivery of a broad range of
molecules including viral antigens, hemoglobin and
insulin.

28. References
• Narang N. Aquasomes: Self-
assembled systems for the
delivery of bioactive molecules.
Asian J Pharm 2012;6:95-100.
• Sanjay S. Jain, Pramod S. Jagtap,
Neha M. Dand; Aquasomes: A
novel drug carrier. Journal of
Applied Pharmaceutical Science
02 (01); 2012: 184-192
• Pandey S., Badola A., Bhatt
G.K.; An overview of
aquasomes. International journal
of pharmaceutical and chemical
sciences, Vol. 2 (3) Jul-Sep
2013;1282 -1287