MAHARSHI ARVIND INSTITUTE OF PHARMACY MAHARSHI ARVIND INSTITUTE OF PHARMACY Mansarovar , Jaipur Mansarovar , Jaipur

Guided by : Prepared by: Mr. Ashok Barupal Jasmin M-pharma

(Department of pharmaceutics)

Aquasomes Aquasomes are water like “Bodies of water” and their water like

properties help to protect and preserve the fragile biological molecules.

comprised of a solid phase nanocrystalline core coated with oligomeric film to which the drug moieties or biologically active molecule are adsorbed with or without modification

Properties of AquasomesProperties of Aquasomes. Aquasomes posses large surface and hence can be sufficient loaded

with the substantial amount of agent through ionic , co-valet , van der walls forces and entropic forces.

Aquasmome mechanism of action is controlled by their surface

chemistry they deliver the content through the combination of specific targeting , molecular shielding , and slow and sustain release process.

Their water like properties provide platform for preserving the

conformational integrity and biochemical stability of bio active moiety .

-:-: Self assembly and self assembled structure Self assembly and self assembled structure :-:-

Nature again exemplified the self assembly i.e Rain drops which is first thermodynamic self assembly.

Molecule are also capable of self assembly. It is the spontaneous association of molecules under equilibrium condition in to stable, structurally well defined aggregate and joined by covalent bond.

It has additional attraction that it generate the structure which occupy the thermodynamic minima.

They are robust and intrinsically very resistant to the incorporation of impurities.

Principle of self assembly.Principle of self assembly. when synthetic product are self assembled?????.....

when the constituent part of that product assume spontaneously prescribe structure orientation in three or two dimensional space…

In aqueous biological environments , the assembly of macro molecule Is governed by three process.

(1) Interaction between charged group.

(2) Hydrogen bonding and dehydration effect.

(3) structural stability.

(1) Interaction between charged group.

Most of the Biological product are charged due to intrinsic chemical group or absorbed ion from the biological milieu.

Interaction of charged group such as amino, carbonyl, sulphate,

phosphate groups facilitate the long rang approach of self assembling sub units.

Natural self assemblies driven strongly by interaction of charged groups include crystal lattice formation bone mineralization. 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

(2) Hydrogen bonding and dehydration 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 such as and α helices and β sheets.

Molecule that form hydrogen bonds are hydrophilic and these

molecules confer significant degree of organization to the surrounding water molecules.

(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 vanderwalls forces largely internal to the molecule

Vander walls forces are largely responsible for the hardness or softness of the molecule. The vanderwalls interaction among hydrophilic side chains promotes stability of compact helical structures

Method of preparation : Method of preparation : By using the principle of self assembly Aquasomes can be prepared By using the principle of self assembly Aquasomes can be prepared

by three method.by three method.

((1) Preparation of core.

(2) coating of core.

(3) Immobilization of drug molecule.

(1) Preparation of core.

This stage mainly depends on the» selection of material for core.

its physical chemical properties

• This can be fabricated by the

» Sonication Sonication

» Colloidal precipitation.Colloidal precipitation.

» Invert magnetron sputtering.Invert magnetron sputtering.

» plasma condensation .plasma condensation .

For the core material ceramic material widely used ,as they are For the core material ceramic material widely used ,as they are structurally most material to be known.structurally most material to be known.

As they are being crystalline their bulk properties is preserved.

Commonly used ceramic core are Diamond and

calcium phosphate.

Example:

synthesis of nanocrystalline tin oxide core material.

this can be prepared by

# Direct current reactive.

# Magnetron sputtering.

3 inch diameter target of highly purified Tin is sputtered 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 70oK with liquid nitrogen

Synthesis of nano crystal brushite (calciumphosphate dihydrate)• This can be prepared by

» colloidal dispersion » Sonication » By reaction of disodium hydrogen phosphate and

calcium phosphate.

• The commonly feature include » Crystalline » They measure b/w 50-150nm. And exhibit clean and

reactive surface

(2) Carbohydrate coating.2) Carbohydrate coating. Process generally entail, Addition of poly hydroxy 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 ultrafilteration.

• Commonly used coating material ,– Cellobiose– Citrate– Sucrose– Trihalose– Pyridoxal -5- phosphate.

(3) Immobilization of drug(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.

Characterization : Size distribution.Size distribution. For morphological characterization and size distribution analysis, (SEM), scanning electron microscopy (TEM ),Transmission electron microscopy 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. For Crystallinity The prepared ceramic core can be analyzed for

its crystalline or amorphous behavior using x-ray diffraction.

• Characterization of coated core. Coating of sugar over the ceramic core can be confirmed by

» Concavalin (determines the amount of sugar coated over core.)» Anthrone method (determines the residual sugar

unbound orResidual sugar remaining after coating). » Zeta potential can also be used.» DSC can be used to analyze the effect of carbohydrate

on the drug loaded to Aquasomes.

• Application : Aquasomes as red blood cell substitute. It can effectively deliver large, complexliable molecule-Hb. Hb, can be immoblized at surface of the degradable,

carbohydrate coated diamond particles and than encapsulated in a standard mixture of phospolipid.

For viral antigen delivery or vaccine. for deliver of the Epstein –Barr virus(EBV) and human immune

deficiency virus (HIV). Delivery of enzymes ,like DNA ase

Antigen delivery.

As oxygen carrier.

Aquasomes for insulin delivery . colloidal precipitation and Sonication of solution Na2HPO4 and Cacl2 prepare Calcium phosphate

dihydrate core.

core further coated with coating material like cellobiose citrate,pyridoxal-5-phosphate, under Sonication .

Drug is loaded to these coated nano particle /Aquasome by partial adsorption mechanism at low temp /Lyophilization

Conclusion: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.

This is probably due to the presence of the unique carbohydrate coating the ceramic. This molecular plasticizer, carbohydrate prevents the destructive drug-carrier interaction and helps to preserve the spatial qualities.

In conclusion, aquasomes appear to be promising carriers for the delivery of a broad range of molecules including viral antigens, hemoglobin and insulin.

However, the roles of molecular plasticizers and core crystallinity need further extensive investigations.

REFERENCES: Jain. N. K. “Advances in controlled drug delivery system”; 317-328. Kossovsky, N.; Gelman, A; Sponsler, E.E.; Hnatyszyn, AJ.; Rajguro,S.;

Torres, M.; Pham, M.; Crowder, J.; Zemanovich, J.; Chung, A andShah, R “Surface modified nanocrystalline ceranlic for drug deliveryapplications.” Biomaterials, (1994a) 15: 1201-1207.