International Journal of Current Research and Review
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IJCRR - 13(4), February, 2021

Pages: 44-52

Date of Publication: 16-Feb-2021


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Aquasomes: A Self-Assembled Nano-Particulate Carrier System

Author: Ajay Kumar Gupta, Diptee Gupta, Vedant Gupta

Category: Healthcare

Abstract:In the last few decades, nanobiotechnology emerged as a novel approach for those drugs that face challenges to deliver in conventional dosage forms. Nanoparticles, liposomes, niosomes, quantum dots and aquasomes are some major different type of nano-biotechnologically developed carrier system. The aquasomesare one of the emerging approach and ideal choice of drug delivery comprises of the nano-particulate self-assembled carrier system. In the development of ceramic nanoparticles, aquasomes proved as a significant drug delivery system. Aquasomes are the three-layered structure, fabricated from the solid crystalline core, coated with carbohydrates on to which biologically active drug molecules are adsorbed. The solid core confers the structural stability, whereas the polyhydroxy oligomer coating protects against dehydration and confers stability to active drug molecules. Formulations of aquasomes are mainly administered by parenteral route but new studies suggest that it could also be administered by other routes. Aquasomes delivers their bioactive molecules via a combination of special targeting molecular shielding and sustained release process. Hydroxyapatite core-based aquasomes are broadly used for the preparation of implants. Aquasomes possess properties of maintaining conformational integrity, and a high degree of surface exposure, which is successfully targeted for the delivery of peptide molecules such as insulin, haemoglobin; enzymes like serratiopeptidase and also aid in targeting vaccine and gene to specific sites. The present article is an attempt to focus on the possible revolutionary applications of aquasomes.

Keywords: Nanobiotechnology, Aquasomes, Carrier system, Novel drug delivery

Full Text:

INTRODUCTION

Aquasomes are nano-particulate carrier system but instead of being simple nanoparticles, these are three-layered self-assembled structures, comprised of a solid phase nano-crystalline core coated with an oligomeric film to which biochemically active molecules are adsorbed with or without modification.1 So “aquasomes” are carbohydrate stabilized nanoparticles of the core which was first developed by NirKossovsky in 1995. Alternatively, aquasomes are termed as “Bodies of Water”, their water like properties support and sustain fragile biological molecules such as polypeptide and proteins. The function of preserving confirmative integrity and a high degree of surface exposure is used to target and deliver bioactive molecules such as peptides and protein hormones, antigens and genes to specific locations where the action is required.2

The aquasomes made up of ceramic core are stabilized by carbohydrates and by using methods like co-polymerization, diffusion or adsorption; the pharmacologically active molecules are incorporated on to the carbohydrate surfaces of preformed nanoparticles.3 Aquasomes composed of three-layered structure: solid crystalline core, carbohydrate coat and the active drug which are self-assembled by non-covalent bonds (Figure 1). The core is coated with polyhydroxy oligomers onto which bioactive molecules are adsorbed. The solid core provides structural ability while carbohydrate coating plays an important role and acts like a natural stabilizer which protects against dehydration and stabilizes the biochemically active molecules.4

Figure 1: Schematic diagram of Aquasome. It has 3 layers. 1. Solid Crystalline Core 2. Polyhydroxy oligomer coat 3. Bioactive molecules.

Aquasomes are spherical 60–300 nm particles. Mainly three types of core materials are used for developing aquasomes i.e. Tin oxide, Nanocrystalline carbon ceramics (diamonds) and Brushite (calcium phosphate dihydrate).  Aquasomes offer an attractive mode of delivery for drugs which are having problems such as route of delivery, physical as well as chemical instability, poor bioavailability and potent side effects.5 The discovery of aquasomes include  concept from food chemistry, microbiology, biophysics and frequent discoveries including solid-phase synthesis, supramolecular chemistry, molecular shape change and self-assembly.6

 PROPERTIES OF AQUASOMES

  • Aquasomes prevent clearance via the reticuloendothelial system or degradation by other environmental problems because of their size and structural stability.

  • Due to its large size and active surface, Aquasomes can be loaded with adequate amounts of agents via non-covalent, ionic bonds, van der Waals and entropic forces successfully.7

  • The mechanism of action of aquasomes is governed by their surface chemistry.

  • The combination of various processes like specific targeting, molecular shielding, and slow and sustained release processes involved in the delivery of the active drug via aquasomes.8

  • Water like properties of aquasomes provides a platform for preserving the conformational integrity and biochemical stability of bio-active.7

  • Aquasomes as a carrier also protects the drug/antigen/protein from harsh pH conditions and enzymatic degradation, thus requiring lower doses.6

PRINCIPLE OF SELF-ASSEMBLY

Self-assembly means that in two or three-dimensional space, the constituent parts of any final product assume the spontaneously prescribed structural orientations. The three-layered structure are self-assembled by non-covalent bonds.7Self-assembly in the aqueous environment of macromolecules have the virtue to design itself in smart nanostructured materials, which is primarily governed by three physicochemical processes;

  1. Interaction between charged groups: Interactions of charged groups such as amino, carboxyl, sulphate, and phosphate-groups, facilitate the long-range approach of self-assembling subunits. From the biological environment, the intrinsic chemical groups or adsorbed ions impart a polarity charge to biological and synthetic surfaces. Most biochemically related molecules are amphoteric molecules.9For the first phase of self-assembly, the long-range interaction of constituent subunits begins at an intermolecular distance of around 15 nm. Long-range forces can extend to 25 nm in the case of hydrophobic structures. Charged groups also play a part in the stabilisation of folded protein tertiary structures.

  2. Hydrogen bonding and dehydration effect: Hydrogen bond plays an important role in base pair matching and help to stabilize the secondary protein structure such as alpha helices and beta sheets. Hydrophilic molecules that form hydrogen bonds, provides the surrounding water molecules with a significant degree of organisation. Whereas hydrophobic molecules unable to form hydrogen bonds, having the ability to repel water molecules from their surroundings to organize the moiety. Organized water decreases the entropy of the surrounding environment. Since it is thermodynamically unfavourable, the molecule dehydrates and get self-assembled.10

  3. Structural stability: In the biological environment, structural stability of protein determined by the interaction between charged group and hydrogen bonds largely external to the molecule and by Van der Waals forces which responsible for hardness and softness of molecule and maintenance of internal secondary structures, provides sufficient softness, allows maintenance of conformation during self-assembly.9Van der Waals forces often experienced by the relatively hydrophobic molecular regions that are shielded from water, play a subtle but critical role in maintaining molecular conformation during self-assembly.11

In the case of aquasomes, sugars help in molecular plasticization.12 Van der Waals forces also play a small but measurable role in the interaction of polypeptides with carbohydrates and related polyhydroxy-oligomers. When molecules change their shape considerably following an interaction, the energy minima assumed upon conformational denaturation tend to block reversal.10

OBJECTIVES OF AQUASOMES

  • The main objective of preparing aquasomes is to protect bio-actives.

  • Aquasomes maintain molecular conformation and optimum pharmacological activity.9

  • Many other delivery systems like pro-drugs, liposomes are prone to destructive interactions between drug and carrier while aquasomes have carbohydrate coating prevents destructive denaturing interaction between drug and solid carriers.13

  • Aquasomes with natural stabilizers like various polyhydroxy sugars act as dehydroprotectant, help in maintaining water-like state and preserves molecules in dry solid-state, protecting from the change in aqueous state, pH, temperature, solvent, salt causing denaturation.8,14

  • An active molecule has characteristics such as unique three-dimensional conformation, freedom of internal molecular rearrangement caused by the freedom of bulk motion molecular interactions, but protein initiates irreversible denaturation when desiccated, even unstable in an aqueous state.10, 14

STRATEGIES USED IN THE CHEMICAL SYNTHESIS OF AQUASOMES

Aquasomes are self-assembled three-layered nanostructure molecules. Hence the strategies involved in chemical synthesis of these nanostructures discussed below.

  1. Sequential covalent synthesis: This strategy is used to produce arrays of covalently linked atoms with well-defined composition, connectivity and shape such as Vitamin B12, it can produce the structures that are distant from the thermodynamic minimum for collection of atoms.15

Covalent polymerization: This strategy is used to prepare molecules with high molecular weight. Low weight substances are permitted to react with itself to yield molecules, including many covalently associated monomers.15 Such as Formation of polyethene from ethylene. Covalent polymerization indirectly provides synthetic routes to stable nanostructures and phase-separated polymers.3

Self-organizing synthesis: This strategy depends on weaker and less directional bonds such as hydrogen, ionic and Van der Waals interactions to assemble atoms, ions or molecules into structures.8 The different types of formulation are prepared by the use of this strategy include molecular crystals, ligand crystals, emulsions, colloids, micelles, self-assembled monolayers and phase-separated polymers. The ion or molecules adjust their position to reach the thermodynamic minimum and get self-organize, during formulation.16

Molecular self-assembly: Self-assembly is a process in which a disorganized structure with pre-existing components forms an organized structure or design. Aquasomes self-assembly has various interesting applications in nanoscience and nanotechnology formulation development.15,16

COMPOSITION OF AQUASOMES

  1. Core material: Widely used core materials are ceramic and polymers. Ceramics such as diamond particles, brushite (calcium phosphate) and tin oxide are crystalline easy to manufacture, biodegradable in nature, low cost and biocompatible. It provides a high degree of order and structural regularity. Due to the high degree of order, higher surface energy yields which leads to efficacious binding of carbohydrate onto it. These properties making it a good candidate for aquasome formulation.17 Polymers such as albumin, gelatin or acrylate are used.18

  2. Coating material: Cellobiose, pyridoxal 5 phosphate, sucrose, trehalose, chitosan, citrate etc. are widely used coating materials. As a natural stabilizer, carbohydrate plays a crucial role and it is preferred mostly. Carbohydrates are adsorbed as a glassy film in nanometre size range coating the preformed ceramic-nanoparticles and self-assembled calcium phosphate dihydrate particles (colloidal precipitation).19The carbohydrate used this purpose are as

  3. Cellobiose: It is 4-O-beta-D-glucopyranosyl-D-glucopyranose reducing sugar. It is acquired from the partial hydrolysis of cellulose. It protects the drug molecule against the dehydration.20

  4. Trehalose: It is an alpha-D-glucopuyranosyl-alpha-D-glucopyranoside non-reducing sugar. Trehalose also shields the drug molecule against dehydration and denaturation. It is observed more effective than cellobiose.20It shown to be tolerant of stress in fungi, bacteria, insects, yeast and some plants. Trehalose acts by protecting proteins and membranes within plant cell during the desiccation process and thus preserves cell structures, inherent flavours, colours and texture.21

Disaccharides like sucrose, trehalose contain a large number of hydroxyl groups and help to replace the water with polar protein residues. Thus it maintains their integrity in the absence of water. Experimental studies done with Calcium transporting microsomes isolated from rabbit muscles and lobster muscles showed that the structure and function of cellular components could be protected by sugar during lyophilisation.22The rehydrated vesicles displays drastically decreased calcium-uptake and uncoupled activity of ATPase when Calcium transporting microsomes are lyophilized without stabilizer sugar. Lyophilized vesicles are morphologically distinct from newly prepared vesicles in presence of as little as 0.3 g of trehalose per g. membrane upon rehydration.21, 23

  1. Bio-active molecules: Drugs which have the property of interacting with the film via non-covalent and ionic interactions proved a good candidate for aquasomes.22

Among three layers of aquasomes, carbohydrate fulfils the objective of aquasomes. The hydroxyl groups on carbohydrate interact with polar and charged groups of proteins, in the same way as with water thus preserve the aqueous structure of proteins on dehydration.23

 METHOD OF PREPARATION OF AQUASOMES

Aquasomes preparation is a very simple and effortless process which require minimum solvent usage and no homogenization steps. By using the principle of self-assembly, the aquasomes are prepared in three steps, i.e., Formation of the core, coating of the core, and immobilization of drug molecule (Figure 2).4

Formation of core material: The first step in the formulation of aquasomes is the development of the ceramic core. The method of ceramic core preparation depends on the choice of core materials. These ceramic cores can be built by various processes such as colloidal precipitation, sonication, inverted magnetron sputtering, and plasma condensation etc.24 In the preparation of core, the most regular material preferred which is ceramic. Two ceramic cores that are generally used diamond and calcium phosphate.

Figure 2: Method of preparation of aquasomes. It involves three steps- a) Ceramic core is prepared first by a different process such as colloidal precipitation, sonication etc. b) In 2nd step ceramic core is coated by polyhydroxy compound c) In 3rd step loading of the drug is done by partial adsorption.

a)  Synthesis of Nanocrystalline tin oxide core

       It can be synthesized by direct current reactive magnetron sputtering. Under a high-pressure mixture of argon and oxygen, the high purity tin is blown from a diameter of 3 inches. Ultrafine particles deposited on a copper tube in a gaseous phase and cooled to 77 K with the flow of nitrogen.3

b) Self-assembled Nanocrystalline brushite (calcium phosphate dihydrate)

It can be synthesized by various processes such as co-precipitation, self-precipitation, sonication and PAMAM methods.

(i) Co-precipitation: Diammonium hydrogen phosphate solution is added dropwise to calcium nitrate solution with continuous stirring. The temperature is maintained at 75°C in a flask bearing a charge funnel, a thermometer, a reflux condenser fitted with a carbon dioxide trap.24, 25The pH of calcium nitrate is maintained 8-10 using the concentrated aqueous ammonia solution. Under the above-mentioned condition, the mixture is magnetically stirred. The precipitates are then filtered, washed and finally dried overnight. In an electric furnace, the powder was sintered by heating to 800–900°C26.

(ii) Sonication: Using ultrasonic bath, the solutions of disodium hydrogen phosphate and calcium chloride were mixed and sonicated. Equivalent moles of both reagents are used. For 2 hrs, the temperature was maintained at 4 °C. The ceramic core is separated by centrifugation and then washed, resuspended in distilled water and filtered. The core material retained on filter paper is collected and dried appropriately.

(iii) Poly (Amidoamine) PAMAM: PAMAM was dissolved in the simulated body fluid of pH 7.4 and placed it for 1 week at 37 °C to induce nucleation and crystal growth. By the addition of the NaOH solution, the pH of the solution was adjusted. The precipitate formed was washed multiple times with deionized water. Then it was filtered and dried overnight.28

c) Nanocrystalline carbon ceramic, diamond particle: These ceramic may also be used for the core synthesis after ultra-cleansing and sonication. The main property of these core is crystalline.3

d) Coating of the core with polyhydroxy oligomer

            Commonly used coating materials are cellobiose, citrate, pyridoxal 5 phosphate, trehalose and sucrose. It is the second step in which ceramic cores are coated with carbohydrates. By the addition of carbohydrate into an aqueous dispersion of the cores under sonication, the coating is carried out. These are then subjected to lyophilization which provides irreversible adsorption of carbohydrate onto the ceramic surface. The unadsorbed carbohydrate is removed by centrifugation.26

e) Immobilization of drug molecule

Loading of the drug to coated particles by partial adsorption is the final step for the preparation of aquasomes. A solution of known concentration of the drug is prepared at suitable pH buffer. Coated particles are dispersed and at low temperature, dispersion is kept at overnight for drug loading or lyophilized.27After sometime drug-loaded formulation obtained, then characterized using various techniques.

FATE OF AQUASOME

            Self-assembled aquasomes are biodegradable nanoparticles that accumulate more in liver and muscles.21 The drug’s pharmacological or biological activity can be accomplished instantly as it is detected without any surface alteration on the surface of the system and cannot find any difficulty in identifying receptor on the active site.29

In vivo studies predict, biodegradation of ceramic is achieved by monocytes and multicellular cells called osteoclasts because they intervene first at the biomaterial implantation site during an inflammatory reaction.30 Two types of phagocytosis process were observed-when cells come in contact with biomaterial; either calcium phosphate crystals were taken up alone and then dissolved in the cytoplasm after the disappearance of the phagosome membrane or dissolution after the formation of the hetero phagosome.31 Phagocytosis of calcium phosphate coincided with autophagy and the deposition of residual bodies in the cell.

EVALUATION PARAMETER OF AQUASOMES

Aquasomes mainly evaluated and characterized by their various morphological and structural property of their core and polyhydroxy oligomer coating structure.

  1.  Evaluation parameter for core material

Size distribution

Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques are used for particle size distribution and morphological analysis.25To determine the particle size, samples were placed on the surface of a specimen stub coated with gold using double-sided adhesive tape in SEM while in case of TEM, particle size is determined after negative staining with phosphotungstic acid.31Coated core, as well as drug-loaded aquasomes are also analysed by these techniques.

Characterization (FTIR)

            Fourier transform infrared spectroscopy (FT-IR) spectroscopy used for determining structural analysis. Potassium bromide sample disk method is used.32 Both the core and coated core can be analyzed by recording their IR spectra in the wavenumber range 4000 - 400 cm1.The characteristic peaks are observed and tally with reference peaks.33Stability of the drug in the formulation can be also determined by this technique.

X-ray diffraction

            To study crystalline or amorphous nature of a material X-ray diffraction study is performed. The hydroxyapatite ceramic core is analysed by exposing the core to copper (Cu), potassium (K) radiation in a wide-angle X-ray diffractometer.30 After that the x-ray diffraction pattern of the sample is compared with the standard diffractogram, based on which the interpretations are made.32In a study, it was observed that calcium phosphate core, lactose individually gave identical sharp peaks for crystalline peaks but when carbohydrate coated cores were observed, peaks represented an amorphous structure.34 It may be the reason for the coating technique (solubilization of carbohydrate insolvent and subsequent drying by lyophilization) and saturation of the surface of the core with carbohydrate (Figure 3).35

Figure 3: Evaluation parameter of aquasomes. Aquasomes consist of 3 layers and all 3 layers are evaluated for evaluation of aquasomes. In the figure, all methods for evaluation of each layer is enlisted.

Evaluation parameter for coated core

Carbohydrate coating: Coating of sugar over the ceramic core can be confirmed by Concanavalin A-induced aggregation method, Anthrone reaction and Phenol sulphuric acid method. In table 1 these methods are described.

Zeta potential measurement

The adsorption of sugar over the core and the prediction of storage stability determined by the measurement of zeta potential. Some studies indicated that with the increase in the saturation process by carbohydrate on to the hydroxyapatite core, the more decrease in zeta potential value.33

Glass transition temperature

Differential Scanning Calorimetry (DSC) studied used to analyse the glass transition temperature of carbohydrates and protein. DSC used to study the effect of carbohydrate on the drug-loaded to aquasomes.34The transition from glass to rubber state can be measured using a DSC analyser as a change in temperature upon melting of glass.

  1. Evaluation parameter of drug-loaded aquasomes

 Drug loading efficiency

It is done to evaluate the amount of drug which is bound on the surface of aquasomes. The drug loading can be determined by incubating the aquasome formulation without the drug in a known concentration of the drug solution for 24 hrs at 4°C.29 After that supernatant is separated by high-speed centrifugation for 1 hrs at low temperature in a refrigerated centrifuge.37Then the clear extractive supernatant is filtered and analyzed free drug content by UV spectrophotometer. The drug payload/drug loading is calculated by the following formula-

% Drug loading=(Weight of total added drug-weight of the unentrapped drug )/(Weight of aquasomes)×100

 In vitro drug release studies

The in vitro release kinetics of the loaded drug is done to study the release pattern of the drug from the aquasomes. Incubate a known quantity of drug-loaded aquasomes in a buffer of suitable pH at 37°C with continuous stirring.35 Samples are extracted from time to time and centrifuged for some periods at high speeds. After each withdrawal, equivalent medium volumes must be substituted. Then supernatants are analyzed to estimate the amount of released drug.38

  1. In-process stability studies

SDS-PAGE (sodium dodecyl sulphate polyacrylamide gel electrophoresis) can be used to assess the stability and integrity of protein during the formulation of the aquasomes.36

ADVANTAGE OF AQUASOMES

  • Aquasomes systems act as a reservoir to release the molecules either in a continuous or a pulsatile manner, avoiding a multiple-injection schedule.39

  • Aquasomes based vaccines offer many advantages as a vaccine delivery system. Cellular and humoral immune responses can be elicited to antigens adsorbed on to aquasomes.36

  • Aquasomes improves the pharmaceutically active agent’s therapeutic effectiveness and defends the medication from phagocytosis and degradation.36

  • These nanoparticles offer a favourable environment for proteins thereby avoiding their denaturalization.

  • Enzyme activity and molecular conformation sensitivity have made aquasome a novel carrier for enzymes such as DNaseand pigment/dyes.

  • Multi-layered aquasomes conjugated with biorecognition molecules such as antibodies, nucleic acid, peptides which are known as biological labels can be used for various imaging tests.39

APPLICATION OF AQUASOMES

  1. Oral delivery of acid-labile enzyme

Rawat et al developed a nanosized ceramic core-based system for oral administration of the acid-labile enzyme serratiopeptidase, prepared by colloidal precipitation under sonication at room temperature coated with chitosan under constant stirring. By further encapsulating the enzyme-loaded core into an alginate gel, the enzyme was secured. The TEM images of particles showed them with a spherical shape and an average diameter of 925 nm.40 Particle enzyme-loading was found to be approximately 46%. Both stability and integrity of enzyme during formulation steps was evaluated by in vitro proteolytic activity. The results revealed these aquasomes protect the structural integrity of enzymes, resulting in a more potent therapeutic effect.31

  1. Insulin and Insulinomimetics delivery

The parenteral delivery of insulin, via aquasomes, done by Cherian et a.l using a calcium phosphate ceramic core. Several disaccharides such as trehalose, cellobiose, and pyridoxal-5-phosphate used for coating the core. The drug loading to the coated cores performed via adsorption process.32The in vivo activity of aquasome formulations of insulin assessed by using albino rats. Pyridoxal-5-phosphate-coated particles found more effective in reducing blood glucose levels as compared to particles coated with Trehalose or Cellobiose. The prolonged activity as a result of the slow release of drug from the carrier as well as the structural stability of the peptide.41

Insulinomimetics aquasomes formulated by colloidal precipitation. Disodium hydrogen phosphate and calcium chloride solution sonicated at low temperature and then cores were coated with disaccharides and immediately loaded with polypeptide- k. In vivo activity evaluated by using albino Wistar rats.42Studies indicated that trehalose coated aquasomes released polypeptide- k faster than cellobiose coated aquasomes. It also reported that polypeptide- k oral delivery did not cause any significant change in serum glucose level.43

  1. Delivery of antigens

The adjuvants usually used to boost the antigen immunity appear either to modify antigen confirmation by surface adsorption or to shield the functional groups. The effectiveness of a new adapted ceramic antigen delivery vehicle is thereby formulated and evaluated by Kossovskyet al. These particles were diamond substrate wrappedin an aqueous dispersion with a glassy carbohydrate (cellobiose) layer and immunologically active surface molecule.38These aquasomes having size range 5–300nm provided both conformational stabilization and a high degree of surface exposure to protein antigen.42 Due to high surface energy, the diamond was the first choice for adsorption and adhesion of cellobiose. It provided a colloidal surface which is capable of hydrogen bonding to the proteinaceous antigen.40 The disaccharide helps to minimize the surface-induced denaturation of adsorbed antigens (muscle adhesive protein, MAP).42

In other studies, BSA (Bovine serum albumin) loaded aquasomes formulated by self-assembling of hydroxyapatite using the co-precipitation method. Trehalose and cellobiose have been used as coating materials. The antigen-loading efficiency was found to be about 20-30%. This BSA loaded aquasomes showed more potent immunological activity compared to that of plain bovine serum albumin, after SC injection.21, 36Aquasomes of malarial merozoite surface protein 119 (MSP-119) were formulated by co-precipitation method using hydroxyapatite nano-ceramic carriers. The small size and large surface area of the prepared hydroxyapatite showed good absorption immunogens efficiency. Slower in vitro antigen release and slower biodegradability activity were also seen in prepared nanoceramic formulations, which may lead to prolonged exposure to antigen-presenting cells and lymphocytes.40,43

d. As oxygen transporter

In one study, hydroxyapatite core was prepared by Khopade et a.l using carboxylic acid-terminated half-generation poly (amidoamine) dendrimers, covered with trehalose trailed by adsorption of haemoglobin.44,45 The particle size, drug loading capacity and oxygen-binding properties of formulation were studied. In vivo studies carried out in rats demonstrated that aquasomes

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Announcements

Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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