Aquasome: A Self-Assembling Supramolecular And Nanoparticulate Carrier System For Bio-Actives

N.K. Hada* and Ashawat M.S.

Laureate Institute of Pharmacy, Kathog, Hamirpur, Himachal Pradesh

*Corresponding Author E-mail: nh.pharma11@gmail.com

ABSTRACT:

Recent advancement within the space of biotechnology and genetics science has resulted in promotion of proteins and peptides as a major class of therapeutic agents. Administration of the bioactive molecules in their active state has been an enormous task to the pharmaceutical additionally as biotechnological industries. Drug associated challenges like appropriate route of drug delivery, physical and chemical instability, poor bioavailability, and potentially serious side effects of these bioengineered molecules are some potential limitations on their successful formulation. While developing these formulations, the goal is to obtain delivery system with optimized drug loading and release properties, long shelf-life and low toxicity. Several types of NDDS have been developed for last few decades which are aquasome, liposomes, niosomes, pharmacosomes, microparticles, nanoparticles, dendrimers, multiple emulsions, microemulsions, osmotic-modulated drug delivery system, transdermal-therapeutic system, self-regulated and brain-targated drug delivery system etc. consider as promising carrier for the delivery of a broad range of molecules includes xenobiotics, viral antigens, haemoglobin and insulin. Whereever medicine area allowed to absorb on the surface of nanoparticales within the presence of carbohydrates film that prevent soft drugs from changing shaped and being damaged when surface bound.

KEYWORDS: Water bodies, Self-assembling carrier system, Nano particulate , Nanocrystalline core, supramolecule, bio-actives etc.

INTRODUCTION:

Aquasome is a colloidal range biodegradable novel drug delivery carrier, primarily based on the principle of self assembly. The aquasome based drug delivery system was first discovered by Sir Nir-Kossovsky. Aquasome containing the particle core composed of nanocrystalline calcium phosphate or ceramic diamond, covered by polyhydroxyloligomeric film. These three layered structures are self assembled by non-covalent bonds (1) (Figure 1). Aquasomes are spherical 60-300 nm particles used for drug and antigen delivery. The active molecular compounds are incorporated by co-polymerization, diffusion or adsorption to carbohydrate surface of preformed nanoparticles (2). Aquasomes are also called “bodies of water”, the term “somes” the cell like formulations of novel drug delivery system (3-4).

Aquasomes delivers their contents through a combination of special targeting molecular shielding and slow and sustained release process. Their intended route of administration is parenteral. Research experts have extended the route of administration from parenteral to oral (5-8). Aquasomes, liposomes, cyclodextrin and dendrimers are the carriers which act as host species by interacting with drug (act as guest molecule) and form special type of supramolecules. The host molecules which made through atoms by covalent interaction whereas the guest molecules interact with host by noncovalent forces and ultimately forms supramolecules (9-10). Supramolecules and nanoparticulate assemblies are desecrated and defined self-assembled structures have successful application in drug delivery system (11-13).

Figure 1: Three layered Self Assembling Aquasome Structure

COMPOSITION OF AQUASOMES

Core material: Ceramic and polymers are most widely used core materials. Polymers such as albumin, gelatin or acrylate are used. Ceramic such as diamond particles, brushite (calcium phosphate) and tin oxide are used (14-15). (Figure 2)

Coating material: Coating materials commonly used are cellobiose, pyridoxal-5 phosphate, sucrose, trehalose, chitosan, citrate etc. Carbohydrate plays important role act as natural stabilizer, its stabilization efficiency has been reported. i.e. fungal spores producing alkaloid stabilized by sucrose rich solution and desiccation induced molecular denaturation prevented by certain disaccharides.

Bio-active: They have the property of interacting with film via non covalent and ionic interactions (16-17).

Fig 2: Formation of aquasome consisting of fabricating a nano crystalline core of a Calcium phosphate (brushite) colloidal precipitate or ceramic diamond.

PROPERTIES AND ADVANTAGE OF AQUASOMES

Aquasomes water like properties preserve the conformational integrity and bio chemical stability of bio-active. Aquasomes mechanism of action is controlled by their surface chemistry (18). Aquasomes possess large size and active surface hence can be efficiently loaded with substantial amounts of agents through ionic, non covalent bonds, vander waals forces and entropic forces. As solid particles dispersed in aqueous environment, exhibit their physical properties of colloids. Aquasomes are mainly characterized for structural analyses, particle size, and morphology these are evaluated by X-ray powder diffractometry, transmission electron microscopy, and scanning electron microscopy (19-21). Aquasomes based vaccines offer many advantages as a vaccine delivery system. Multilayered aquasomes conjugate with bio recognition molecules such as antibodies, nucleic acids, peptides which are known as biological labels can be used for various imaging tests. These systems act as a reservoir to release the molecules either in a continuous or a pulsatile manner, avoiding a multiple injection schedule. They increase the therapeutic efficacy of active molecular compounds and protect the drug from phagocytosis and degradation (22-23).

PRINCIPLE AND FORMULATION OF AQUASOMES

Self assembly implies “the constituent parts of some final product assume spontaneously prescribed structural orientations in two or three dimensional space”. The self assembly of macromolecules in the aqueous environment, either for the purpose of creating smart nanostructure materials or in the course of naturally occurring biochemistry, is governed basically by three physicochemical processes: the interactions of charged groups, dehydration effects and structural stability (24, 26).

Interactions between Charged Groups: The interaction of charged group facilitates long range approach of self assembly sub units charge group also plays a role in stabilizing tertiary structures of folded proteins. The interactions of charged groups such as amino-, carboxyl-, sulphate-, and phosphate-groups, facilitate the long range interaction of constituent subunits beginning at an intermolecular distance of around 15 nm, is the necessary first phase of self assembly.

Hydrogen Bonding and Dehydration effects: Hydrophobic molecules, which are incapable of forming hydrogen bond, their tendency to repel water helps to organize the moiety to surrounding environment, organized water decreases level of entropy and is thermodynamically unfavourable, the molecule dehydrate and get assembled.

Structural Stability: Structural stability of protein in biological environment determined by interaction between charged group and hydrogen bonds largely external to molecule, provides sufficient softness, allows maintenance of conformation during self assembly. Vander waals forces play a critical role in maintaining molecular conformation during self assembly in the interaction of polypeptides with carbohydrates and related polyhydroxyoligomers (24).

The general procedure consists of an inorganic core formation, which will be coated with lactose forming the poly hydroxylated core that finally will be loaded by model drug. The core is coated with a polyhydroxyloligomeric film, and the coated particles are then allowed to adsorb a drug or antigen. The final product consists of three layers: drug, polyhydroxyloligomeric film, and nanocrystalline ceramic core. The aquasomes are prepared using the principle of self-assembly, the aquasomes are prepared in three steps i.e., (A) preparation of core, (B) coating of core, and (C) immobilization of drug molecule. (23-24). (Figure 3)

METHODS FOR CHARACTERIZATION OF AQUASOMES:

Characterization of Aquasomes:

Size distribution: Morphological properties and particle size distribution can be characterized by scanning electron microscopy and transmission electron microscopy. For the measurement of man particle size and zeta potential of the particle photon correlation spectroscopy is used.

· Structural analysis: In FT-IR, Potassium bromide sample disk method is used, core as well as coated core is analysed by recording their IR spectra in wave number range 4000-400 cm.

· Crystallinity: X-ray diffraction is used to determine crystalline behaviour of ceramic core.

Characterization of Coated Core: For coating of sugar over ceramic core - Concanavalin A-induced aggregation method or anthrone method is used. By the help of zeta potential measurement, absorption of sugar over the core is recorded. Glass transition temperature- The transition from glass to rubber state as a change in temperature upon melting of glass DSC analyser can be used to analyse.

Characterization of Drug-Loaded Aquasomes

· Drug payload: It is determined by measuring the drug in the supernatant liquid after loading which can be estimated by analysis method.

· In vitro drug release studies: The release pattern of drug from the aquasome is determined by incubating a known quantity of drug loaded aquasome in pH at 37 ͦ C with continuous stirring. The sample is withdrawn and centrifuge at high speed for certain length of time which is later on analysed. (25-26)

Table 2: FDA Approved Recombinant Proteins delivered through aquasomes

Trade Name	Recombinant Product
Activase	Tissue plasminogen activator
Cerezyme	Glucocerebrosidase
Epogen/procrit	Erythropoietin
Fabrazyme	Galactosidase a
Gonal-f	Follicle stimulating hormone
Herceptin	Anti-HER 2 humanized mAb
Luveris	Luteinizing hormone
Myozyme	Acid –glucosidase
Novoseven	Clotting factor VII a
Ovidrel	Human chronic gonadotropin
Raptiva	Anti-CD11a humanized mAb
Recombinate	Clotting factor VIII
Simulect	Anti-IL2receptor-chimeric mAb
Thyrogen	Thyro tropin
TNKase	Tissue plasminogen activator

CONCLUSION:

Various novel delivery systems used as carriers for various pharmaceutical applications are listed in Table 3. Aquasomes provide mode of delivery for therapeutic agent e.g. proteins and peptides (Table 1, 2). They consist of a ceramic core whose surface is non-covalently modified with carbohydrates to obtain a sugar ball, which is then exposed to adsorption of a therapeutic agent. Since these are able to overcome some inherent problems associated with these molecules. The problems include suitable route of delivery, physical as well as chemical instability, poor bioavailability, and potent side effects.

Table 3: Different approaches used for Novel drug delivery system (NDDS) (27-29).

Carrier	Description	Application
Cryptosomes	Lipid vesicles with a surface coat composed of PC, of suitable polyoxyethylene derivative	Ligand-mediated drug targeting
Emulsomes	Nano sized lipid particles consisting of microscopic lipid assembly with a polar core	Parenteral delivery of poorly water soluble drugs
Enzymosomes	Liposomes designed to provide a mini bioenvironment, enzymes are covalently immobilized or coupled to surface of liposomes	Targeted delivery to tumor cells
Photosomes	Photolyase encapsulated in liposomes, release the contents	Photodynamic therapy
Aquasomes	Three layered self-assembly compositions with ceramic nanocrystalline core loaded.	Molecular shielding, specific targeting
Archaeosomes	Vesicles composed of glycerol lipids of Archaea with potent adjuvant activity	Potent adjuvant activity

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Received on 11.12.2013 Modified on 20.12.2013

Res. J. Pharm. Dosage Form. & Tech. 6(1): Jan.-Mar. 2014; Page 50-53

Use	Protein/ Surface	Rational Macromolecules
Vaccines	Antigenic envelope	To be effective protein protective antibodies must raised against conformationally specific target mole.
Blood Substitutes	Haemoglobin	Physiological binding and release of oxygen by haemoglobin is conformationally sensitive.
Pharmaceuticals Pigments/ dyes	Active drug Dye agents	Drug activity is conformationally specific wavelength absorption and reflection/ cosmetics properties of natural pigments
Enzymes	Polypeptide	Activity fluctuates with molecular conformation. Gene therapy, Genetic Targeted,