2. REVIEW OF LITERATURE
2.1. Development of Aquasomes
The adjuvants generally used to enhance the immunity to antigens have got tendency either to alter the conformation of the antigen through surface adsorption or shield the functional groups. Kossovsky et al. (1995) through a combination of material science, surface chemistry and biology, demonstrated the efficacy of new organically modified ceramic antigen delivery vehicle. These particles consisted of diamond substrate coated with a glassy carbohydrate (cellobiose) film and an immunologically active surface molecule in an aqueous dispersion. These modified nanoparticles (5-300 nm) provided conformational stabilization as well as high degree of surface exposure to protein antigen. Diamond, being a high surface energy material, was expected to be thermodynamically favourable choice for adsorption and adhesion of cellobiose onto the aquasomes prepared from it. It was resulted in colloidal surface capable of hydrogen bonding to the proteinaceous antigen to be adsorbed subsequently. Moreover, the disaccharide could act as dehydroprotectant and help to minimize surface-induced denaturation of adsorbed antigens (muscle adhesive protein, MAP). For MAP, conventional adjuvants had proven only marginally successful in evoking an immune response. However, with the help of these surface modified diamond nanoparticles, a strong and specific immune response could be elicited by enhancing the availability and in vivo activity of antigen.
In 1996, Kossovsky et al. studied carbon ceramic nanoparticles and self assembled calcium phosphate dihydrate particles to which glassy carbohydrates are then allowed to adsorb as a nanometer thick surface coating to form a molecular carrier. The carbohydrate coating functions as a dehydroprotectant and stabilizes subsequently non-covalently bound immobilized members of biochemically reactive surface members such as pharmaceuticals.
In 2000, Cherian et al. prepared aquasomes using calcium phosphate ceramic core for the parenteral delivery of insulin. The core was coated with different disaccharides like cellobiose, trehalose and pyridoxal-5-phosphate and subsequently the drug was loaded to these particles by adsorption method. The in vivo performance of various aquasome formulations of insulin were evaluated in albino rats. Prolonged reduction of blood glucose was observed with all formulations except cellobiose coated particles. Moreover, pyridoxal-5-phosphate coated particles reduced blood glucose more effectively as compared to trehalose and cellobiose coated aquasomes. This could be attributed to high degree of molecular preservation provided by pyridoxal-5-phosphate. The prolongation of activity may be the result of slow drug release form the carrier and structural integrity i.e. without denaturation or dehydration effects during delivery and storage. This work recommended the aquasomes as a promising carrier for therapeutic proteins and peptides drug delivery by virtue of protecting their structural integrity and thus exhibiting better therapeutic efficacy.
Hydroxyapatite is a biodegradable material that forms a major component of bones and teeth. Paul and Sharma (2001) prepared porous hydroxyapatite nanoparticles entrapped in alginate matrix containing insulin for oral administration. They observed the desirable controlled release of insulin and thus further signified the use of ceramic nanopartiles as delivery vehicles for the proteins and peptides.
Khopade et al. (2006) prepared hydroxyapatite core by using carboxylic acid terminated half generation poly(amidoamine) (PAMAM) dendrimers as templates or crystal modifiers. These cores were further coated with trehalose followed by adsorption of haemoglobin to obtain aquasomes. The size of the particles was found to be in nanometric range and the particles were able to load approximately 13.7 mg of haemoglobin per gm of the core. The oxygen binding properties of the aquasomes were studied and
