INTRODUCTION:

In the past decade, a variety of technical approaches have been put out to produce unique nanoparticles that are loaded with medication. This has completely transformed drug delivery systems, especially those that are focused on controlled release and the active principle's vectoring for release at the organs or target tissue (Bharatee Chaudhari et al., 2014). Polymers are employed in a variety of ways to prepare nanoparticles, and these procedures often run into issues with solvent compatibility, the compatibility of the polymers and co-polymers with the active principle, biological fluids, and collection system variables, among other issues (Oviedo et al., 2007).

Kossovsky developed a method for creating nanoparticles that include what are known as aquasomes (Kossovsky et al., 1995), Its particle size (less than 1000 nm) is suitable for parenteral delivery since it avoids obstructing the capillaries in the bloodstream (Junju et al., 2013).

Comparably to "bodies of water," aquasomes are made of water and are used to protect and preserve sensitive biological components. They are also capable of preserving structural integrity. Elevated surface exposure is employed to direct bioactive substances, including as enzymes, antigens, peptide and protein hormones, and genes, to specific sites. Ionic and non-covalent bonding allows these three-layered structures to self-assemble. We call these carbohydrate-stabilizing ceramic nanoparticles "aquasomes." the pharmacologically active substance that is added by co-polymerization, diffusion, or adsorption to the carbohydrate surface of pre-formed nanoparticles. A principle from food chemistry, biophysics, and microbiology is combined with several other discoveries, including supramolecular chemistry, solid phase synthesis, molecular shape change, and self-assembly, to discover aquasomes (Jain et al., 2001).

The concept of "safe and effective delivery of pharmaceuticals" refers to the practice of administering medications only at the cell's targeted place and only in accordance with its intended purpose. It is commonly accepted that the structural and functional properties of molecules exhibiting pharmacological activity are determined by their molecular makeup. A change in chemical composition usually results in the loss, degradation, or alteration of natural structural and functional properties. It is possible that this information is not widely known, but these pharmacological molecules' composition results in three activity-related spatial properties that they display in their natural (active) state: a unique three-dimensional conformation, freedom of bulk movement, and freedom of internal molecular rearrangement caused by intermolecular interactions (Figure 1). Thus, it stands to reason that a pharmacologically Each of these three activity-related spatial features lost by an active molecule will result in the generation of one of several Potential alternative conformations are also associated with the degradation, alteration, or loss of fundamental structural and functional properties (Kossovsky N et al.,1994).

The nanoparticulate carrier system is one of the self-assembling techniques for the delivery of bioactive materials. Ceramics and polymers both lend themselves to the creation of nanoparticles. By adsorption to the preform nanoparticulate's surface, diffusion into the pre-assembled nanoparticulate matrix, or co-polymerization inside the self-assembling nanoparticulate matrix, the pharmacologically active chemical can be introduced to them. Polymeric nanoparticles can be made from both quasi-biological materials, such as albumin or gelatin, and organic compounds, such as acrylates (Kossovsky N et al., 1993).

Figure: 1

Composition of Aquasomes:

1. Core material:

The utilization of core materials Gellatin, acrylate, and albumin are effectively bound to the coating material by brushite (calcium phosphate) and disodium hydrogen phosphate (polymer). Since it is easily manufactured and ceramics are biodegradable, hydroxyapatite is also utilized in the fabrication of aquasomes. For structural regularity, carbohydrates have a high surface energy or considerable potential. The natural occurrence of calcium phosphate in the human body has advantages (Kaur et al., 2015).

2. Coating material:

The preparation material for coating aquasomes is commonly used to coat lactose, sucrose, chitosan, pyridoxyl-5 phosphate, and carbohydrates. The carbohydrate coating acts as a natural stabilizer and is crucial for the adsorption glassy film in ceramic nanoparticles. Additionally, the coating stabilizes the core material, and the ratio of core to coat depends on the aquasome's particle size. By creating a water-like environment, bioactive can maintain the structural integrity of proteins. The self-assembling calcium phosphate particles are utilized in the coating process (Khopade et al., 2002).

Method of preparation:

The three stages of aquasome production—core preparation, core coating, and drug molecule immobilization—all stem from the idea of self-assembly. All agree that the aquasome is an aqueous colloidal composed of minute solid particles formed by a small number of atoms packed together in solid crystals, which are then coated with glassy carbohydrates on their surface. With the active drug candidate attached, the carbohydrate-coated core serves as a non-denaturing solid phase that confers distinct properties to each of the final colloidal qualities.

a) Preparation of the Core:

Making the ceramic core is the initial stage in the preparation of aquasomes. The choice of core materials affects the ceramic core preparation process. These ceramic cores can be made using a variety of techniques, including plasma condensation, inverted magnetron sputtering, colloidal precipitation and sonication, and others. Because ceramic is the most regular material known in terms of structure, ceramic materials were commonly employed for the core (Allemann E et al.,1993).

1. Synthesis of Nanocrystalline Tin Oxide Core Ceramic:

Reactive magnetron sputtering with direct current is one method of synthesis. Here, a high purity tin target with a diameter of 3 inches is sputtered in a high-pressure gas mixture containing oxygen and organ. Following the gas phase, the ultra-fine particles are gathered on copper tubes that have been cooled to 70°K while nitrogen is flowing through them (Bharatee Chaudhari et al., 2014).

2. Self-assembled Nanocrystalline Brushite (Calcium Phosphate Dehydrate):

These can be made by sonicating a solution of disodium hydrogen phosphate and calcium chloride, followed by colloidal precipitation (Bharatee Chaudhari et al., 2014).

3. Nanocrystalline Carbon Ceramic, Diamond Particles:

These can also be employed, following ultra cleaning and sonication, for the core synthesis. All of the different cores have one thing in common: they are crystalline, measure between 50 and 150nm, and have incredibly clean, reactive surfaces when added to the synthetic processes (Norde W et al., 1992).

b) Carbohydrate Coating:

The second steps involve coating by carbohydrate on the surface of ceramic cores. There are numbers of processes to enable the carbohydrate (polyhydroxy oligomers) coating to adsorb epitaxially on the surface of the nanocrystalline ceramic core. The processes generally entail the addition of poly hydroxy oligomer to the dispersion of meticulously clean ceramics in ultra-pure water, sonication and then lyophilization to promote the largely irreversible adsorbtion of carbohydrate on to the ceramic surfaces. Excess and readily desorbing carbohydrate is removed by stir cell ultrafiltration. The commonly use coating materials are cellobiose, citrate, pyridoxal-5-phosphate, sucrose and trehalose (jain N K 2001).

1. Cellobiose:

4-0-β-D- Glucopyranosyl-D- glucose; β-cellobiose; cellose; 4-( β-D- glucosido)-D-glucose. Molecular wt-342.30, Unit of cellulose and lichenin. Does not occur free in nature, or as glucoside, Preparation from cotton, preparation from cell-free enzymatic hydrolyzate of cellulose. Minute crystals from dil alcohol which retain 0.25 to 0.50mol water after drying in vacuum. Indifferent taste., Dec 225° shows mutarotetion. 1 gm dissolves in 8 ml water, in 1.5ml boiling water. Almost insoluble in absolute alcohol and ether. Reduces Fehling solution Hydrolysis with acid or emulsion yields 2mols β-D- glucose. Not fermented by brewer’s yeast, maltase or invertase. Cellobiose is a disaccharide that has been used to assess intestinal permeability. It has been used as an alternative to lactulose in the differential sugar absorption test (Bharatee Chaudhari et al., 2014).

2. Trehalose:

α-D-Glucopyranosyl- α-D glucopyranoside; α- α-terhalose; natural terhalose; mycose; (α-D-glucosido)- α-D- glucoside. Molecular wt-342.30 about 23-30% is found in trchalamanna, the cocoons of a parasitic beetle (Larinus species) found on Echinops pesicus. Trehalose also occurs in fungi; e.g. Amanita muscaria. Dihydrate, orthorhombic, bisphenoidal crystals from dil alcohol. Sweet taste, The water of crystallization escapes around 130°, Anhydrous Trehalose melts at 203°, Soluble in water, hot alcohol. Insoluble in ether. Does not reduce Fehling solution. Is fermented by yeast. Is not split by α-glucosidase. Acid hydrolysis gives 2 mols D- glucose ( Budavari S,1996 and Kathleen Parfitt, 1561).

c) Immobilization of Drug:

For a wide variety of biochemically active molecules, the surface-modified nanocrystalline cores supply the solid phase needed for the ensuing non-denaturing self assembly. Partial adsorption can be used to load the medication. As an illustration: Making aquasomes of Indomethacin. The general process involves the production of an inorganic core, which is then covered with lactose to create a polyhydroxylated core, which is then loaded by the model drug, indomethacin. The 0.25M monobasic sodium phosphate solution and the 0.75M mechanically agitated calcium chloride solution precipitated to get the inorganic cores made from calcium phosphate. After 90 minutes of mechanical stirring, 1.0mg of the inorganic cores were resuspended in 1.0ml bi-distilled water and put to a 100ml lactose solution.After agitation, the mixture was passed through a nitrocellulose membrane filter with a pore size of 0.22 μm, and the resulting polyhydroxylated nanoparticles were produced by lyophilization. Following a mechanical agitation that lasted for ninety minutes, a 0.06M solution of Indomethacin in acetone was added at a dispersion of 1mg/ml of the polyhydroxylated cores. After filtering, the dispersion was freeze-dried (Irma Rojas-Oviedo et al., 2007).

Evaluation of Aquasomes:

1. Size distribution

2. Structural analysis

3. Crystallinity

4. Glass transition temperature

5. Mean particle size and Zeta potential

6. Drug loading efficiency

7. In vitro drug release study

1. Size distribution:

The use of transmission and scanning electron microscopes (SEMs) for the morphological examination or size distribution of aquasomes. These two methods are used to assess the coated core: electron photon spectroscopy is used to determine the zeta potential, and the SEM particle size is applied to the surface of the gold-coated sample with two sides so that it can be seen under magnification. The particle is determined to be negatively stained in 1% phosphotungstic acid using a TEM transmission electron microscope, and photos are captured in both clear and dark modes on photographic film produced using Adobe software (Prasanthi et al., 2010).

2. Structural analysis:

FT-IR Fourier transform infrared spectroscopy can be used in the structural investigation of aquasomes to identify the sample's core material through the potassium bromide disk method. By using FTIR analysis, which records wave numbers between 200 and 400nm, coating material identity and conformation are determined. Particles move from lower to higher wavelengths, revealing the creation of hydrogen bonds in molecules (Jain et al., 2009).

3. Crystallinity:

Using X-ray diffraction (XRD) analysis, the crystalline or amorphous characteristics of the ceramic core are assessed. Based on diffractogram interpretations, this approach noticed that the calcium phosphate core is same and that the coated core is crystalline. Following coating, the polysaccharide's core comprises amorphous pyridoxyl-5-phosphate peak, lactose, sucrose, and trehalose. In addition to anthrone, polysaccharide hydrolyzes to monosaccharide.

4. Glass transition temperature:

Using differential scanning calorimetry, which is employed in glass transition temperature, the carbohydrate content of drug-loaded aquasomes is ascertained or measured. DSC measures the temperature shift and glass melting point at the glass to rubber transition. In order to use differential scanning calorimetry, the formulation is placed in the sample cell and the buffer is placed in the reference cell (Rakesh et al., 2012).

5. Mean particle size and zeta potential:

Zeta potential, a particle size analyzer, determines the drug-loaded aquasomes or their particle size (Zetasizer). For the purpose of measuring zeta potential, the sample is dissolved in distilled water or another solvent. The formulation penetrates deeply into the zeta dip cell. The study shows that the lactose process that contains carbohydrates saturates the zeta potential, lowering its value (Senapati et al., 2018).

6. Drug loading efficiency:

Drug loading is done using an aquasome formulation with a known drug concentration in the solution. Weigh the medication accurately, let it sit at 4°C for 24 hours, then spin the liquid supernatant for 30 minutes at a low temperature and store the solution in the refrigerator. The drug-loading formula is below after the clear solution has been filtered and examined with a UV spectrophotometer.

Weight of total drug added - Weight of an entrapped drug

% Drug loading = -------------------------------------- × 100

Weight of aquasomes

7. In vitro drug release study:

The drug-loaded aquasome formulation used in the in vitro release investigation uses a pH 6.5 phosphate buffer and 900cc of dissolving fluid in a USP type 1 dissolution test device. 50mg of aquasome powder should be weighed, then the gelatin capsule should be filled with it and the media should be swirled at 100rpm and 37°C. A 100ml sample is added at different times, and after a short while, 10ml of the sample is taken out of the basket and set aside for centrifugation, which takes 15 minutes. Using a UV spectrophotometer, the filtered solution and precipitate are measured at 340 nm, and 10milliliters of fresh dissolution media are used to preserve the results (Vyas et al., 2008).

Application of Aquasomes:

The use of aquasomes Ceramic particle-containing aquasomes facilitate the release of an acid-labile chemical and improve the solubility or stabilizer in a medication with low solubility. The other study finds that vaccinations, viruses, and antigens raise the rate of breakdown and shield bioactive chemicals. After being applied to aquasomes.

1. Vaccines or viral antigen delivery (Shirsand et al., 2012).

2. Delivery of enzymes (Shukla et al., 2016).

3. Delivery of oxygen (Shukla et al., 2016).

4. Using aquasomes to administer insulin (Sutariya et al., 2012).

5. As an alternative to red blood cells (Umashankar et al., 2010).

6. Gene transfer (Wilczewska et al., 2012).

Advantages:

1. Higher drug bioavailability for prescription drugs such BCS Class II (Gholap et al., 2011).

2. It has overcome the difficulties brought forth by the drug's rapid solubility or degradation.

3. Drugs that are hydrophilic or lipophilic can both be added to the aquasomal combination.

4. It increased the stability of the formulation.

5. It reduces side effects and pharmaceutical toxicity.

6. The prolonged half-life of the medication in the bloodstream.

7. Acts as a vehicle for vaccination delivery.

8. Aquasomes retain the conformational integrity and the biological stability of the bioactive chemicals.

Future Area:

The goal of the recent development of aquasomes for medication delivery has been to lessen the toxicity of drugs, improves shelf life and the targeted chemical.

CONCLUSION:

Better biological activity is demonstrated by the aquasomes, and they also have excellent solubility or boosting properties. intended side. The purpose of the carbohydrate coat is to preserve the bioactive molecules or drug interactions in the formulation. It focuses on innovative drug delivery methods to address the limitations associated with pharmacological agents. The crystalline form of the aquasome core provides stability, a wide spectrum of molecular delivery, and improved immunological response in the immune system. It also delivers hemoglobin blood replacements, insulin, or enzyme delivery.

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Received on 26.02.2024 Modified on 18.03.2024

Asian J. Research Chem. 2024; 17(2):119-123.

DOI: 10.52711/0974-4150.2024.00023