International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - Vol 03 Issue 03, March, 2011

Pages: 73-80

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PRODRUGS: AN APPROACH TOWARDS BETTER TARGETTING

Author: Mayank Yadav, Himani Bajaj, Vinod Singh, Mamta Singh

Category: Healthcare

Abstract:Prodrugs, the pharmacologically inactive derivatives of active drugs, are designed to maximize
the amount of active drug that reaches its site of action, through manipulation of the
physicochemical, biopharmaceutical or pharmacokinetic properties of the drug. But new
developments are increasingly taking the concept beyond issues of availability to include
targeting. The development of prodrugs promises to be very effective method for treatment of
diseases in future. This approach has several advantages over conventional drug administration.
In this mini review, prodrugs are discussed with a focus on the viability of the prodrug approach
as a means of attaining targeted drug delivery. Next, several examples of where the prodrug
approach has been used to achieve targeted delivery will be discussed.

Keywords: prodrugs, targeting, targeted drug delivery.

Full Text:

INTRODUCTION

A drug can be defined as a chemical used for treating, curing or preventing disease in human beings or in animals. In the process of treatment, drugs are also used for medical diagnosis and for restoring, correcting, or modifying physiological functions. Conventional drugs suffer from many drawbacks in their performance like site specificity, permeability and resistance. Almost all drugs possess some undesirable physicochemical and biological properties. Their therapeutic efficacy can be improved by minimizing or eliminating the undesirable properties while retaining the desirable ones 1 . This can be achieved through following means. • The biological approach is to alter the route of administration which may or may not be acceptable to patient. • The physical approach is to modify the design of dosage form such as controlled drug delivery of drug. • The third and best approach in enhancing drug selectivity while minimizing toxicity is the chemical approach for design of prodrugs 2 .

The Prodrug Concept

Albert and his coworkers were the first ones to suggest the concept of prodrug approach for increasing the efficiency of drugs in 1950. They described prodrugs as pharmacologically inactive chemical derivatives that could be used to alter the physicochemical properties of drugs, in a temporary manner, to increase their usefulness and/or to decrease associated toxicity2 .Subsequently such drug-derivatives have also been called „latentiated drugs?, „bioreversible derivatives?, and „congeners?, but „prodrug? is now the most commonly accepted term. Thus, prodrug can be defined as a drug derivative that undergoes biotransformation enzymatically or nonenzymatically, inside the body before exhibiting its therapeutic effect. According to IUPAC (International Union of pure and applied chemistry): Prodrug is defined as any compound that undergoes biotransformation before exhibiting its pharmacological effects 3 .

Characteristics of a Prodrug In recent years numerous prodrugs have been designed and developed to overcome barriers to drug utilization such as

4 : ? Low oral absorption properties

? Lack of site specificity

? Chemical instability

? Toxicity ? Bad taste

? Bad odour

? Pain at application site 4, 5

Ideal properties of prodrug It should have intrinsic pharmacological activity that means it should not change receptor configuration that is necessary for pharmacological response. It should rapidly transform into the active from where desired and metabolic fragment, apart from the active drug should be nontoxic 6 .

Limitation of prodrug 7 The problem associated with prodrug design is its toxicity which is due to Formation of unexpected metabolite from the total drug conjugates. Toxicity may be due to inert carrier generated by cleavage of promoiety and drug conjugate which is converted into toxic metabolite. The prodrug might consume a vital cell constituent such as glutathione during its activation stage which causes depletion of prodrug 8 .

Classification of Prodrugs A)

Carrier linked prodrug Contain a group that can be easily removed enzymatically (such as ester) to reveal the true drugs as shown in fig.1.Ideally the group removed is pharmacologically inactive and nontoxic while the connecting bond must be labile for efficient activation in vivo. Prodrugs are the ones where the active drug is covalently linked to an inert carrier transport moiety. They are generally esters or amides. Such prodrugs have greatly modified lipophilicity due to the attached carrier and the active drug is released by hydrolytic cleavage, either chemically or enzymically 9 . It can be further subdivided intoBipartate- Composed of one carrier (group) attached to the drugs. Tripartat- Carrier group is attached via linker to drug. Mutual Prodrugs- Two drugs linked together.

B) Bio precursors Metabolized into a new compound that may itself be active or further metabolized to an active metabolite as shown in fig.2 (e.g. amine to aldehyde to carboxylic acid) 10

PRODRUG MEDIATED TARGETED DELIVERY

Targeting viruses

The topic of targeted delivery of antiviral agents has been recently reviewed 11. One of the best and simplest examples of targeted drug delivery via a prodrug approach is the antiviral agent. Acyclovir (9-(2- hydroxyethoxymethyl) - guanine). As shown in Fig. 3, its targeting is achieved primarily by site-selective activation. The herpes virus encoded enzyme, pyrimidine deoxynucleoside (thymidine) kinase, is responsible for converting acyclovir to its phosphate monoester. Subsequently, cellular enzymes catalyse the conversion of the monoester to the di- then triphosphorylated species. This latter species is the pharmacologically active one, and the enzymatic conversion to triester occurs to a significantly greater extent in the herpesinfected cells. Because of its site-specific activation, acyclovir displays a high therapeutic activity against herpes virus, essentially no activity against adenovirus, minimal metabolic degradation following systemic administration, and very low toxicity against uninfected host cells 12, 13.

Targeting the colon

A fundamentally simple example of targeting which exploits both site-specific transport and activation is the colon-specific delivery of drugs illustrated in Fig. 4. With this approach, prodrugs are formed by coupling the drug to a hydro- philizing promoiety that is susceptible to cleavage by enzymes secreted by the bacterial microflora associated with the lower gastrointestinal tract 14 . Following oral administration of the prodrug, drug absorption in the stomach and small intestines is decreased due to the polar nature of the promoiety; therefore, greater levels of the drug, in the form of the prodrug, can reach the colon. Within the colon, the bacterially derived enzymes catalyze the conversion of the prodrug to the more lipophilic drug which is now available for absorption through the colonic membrane. This targeting concept has been recently reviewed Glycosidic and glucuronidic prodrugs, of agents such as dexamethasone, naloxone, and menthol, that exploit bacterial glycosidases and glucuronidases have been studied for their colon-targeting potential 15 .

Targeting the kidney

Site-selective prodrug activation, by exploiting the relatively high response site activity of an enzyme, has also been achieved with targeted delivery to the kidney. For example, dopamine was found to selectively accumulate in the kidney following the intraperitoneal administration of the double prodrug, y-glutamyl-L-dopa, to mice 16. As shown in Fig. 5, the prodrug is activated by the sequential catalytic actions of two enzymes that possess high activity in the kidney. First, y-glutamyl transpeptidase catalyzes the cleavage of the y-glutamyl linkage: the L-dopa which is formed is then decarboxylated to dopamine by L-amino acid decarboxylase. The end result is that dopamine is more readily available to exert its therapeutic effect (i.e., renal vasodilation) at the response site while causing less effects at non-response sites (as was demonstrated by an unchanged systemic blood pressure).

Targeting the liver

To achieve targeted drug delivery to the liver, researchers have attempted to exploit site-selective transport pathways. One such pathway is the bile acid transport system associated with the sinusoidal membrane of hepatocytes 17. The bile acid prodrugs of several compounds, such as chlorambucil, thyroid hormone (L-T). and HMG-CoA reductase inhibitors 18 have demonstrated some degree of hepatic targeting.

Targeting the brain

To preferentially deliver amine-containing drugs to the brain 19 have developed a prodrug delivery system which exploits the oxidative conversion of a dihydropyridine promoiety to its corresponding pyridinium salt (Fig. 6). With this approach, an aminecontaining drug is coupled to a lipohilic dihydropyridine promoiety that facilitates the penetration of the drug, in the form of the prodrug, through the blood-brain barrier (BBB). Oxidation of the dihydropyridine functionality in the peripheral compartments results in the formation of the corresponding polar pyridinium salt which can be readily excreted from the body, whereas formation of the pyridinium salt in the CNS results in site retention because of the poor permeation characteristics of the charged species and the permeability characteristics of the BBB. Subsequent cleavage of the pyridinium salt promoiety releases the drug which is now present at elevated levels within the brain. The proof-of concept has been has been demonstrated for a wide variety of aminecontaining drugs.

Targeting with antibodies

Selective activation of a prodrug of an anticancer agent at tumor sites is severely limited by the commonality of enzymes associated with normal and neoplastic tissues. Therefore, two approaches utilizing monoclonal antibodies20 have been studied as a way of selectively activating a prodrug at the tumor site. These approaches, which have received considerable attention over the last decade, are Antibody- Drug Conjugates and Antibody-Directed Enzyme Prodrug Therapy (ADEPT). Antibody-drug conjugates Antibody-drug conjugates (immune conjugates) are macromolecular prodrugs that are formed by covalently linking cytotoxic agents to monoclonal antibodies reactive with tumor associated antigens. A number of chemical coupling methods have been utilized to produce the drug-antibody conjugates, and several tumor-associated antigens have been identified, and the respective monoclonal antibodies have been produced. In order for targeting to be achieved, the drug must be cleaved from the antibody after the immune conjugate binds to a tumor cell; this usually occurs intracellularly (e.g. lysosomal degradation) after internalization of the conjugate Fig. 7a shows a simplified depiction of this process 21 .

Antibody-directed enzyme prodrug therapy (ADEPT)

A simplified scheme of the ADEPT approach to targeted drug delivery is shown in Fig. 7b. Ideally, administration of an enzyme, which is covalently linked to a monoclonal antibody, binds selectively to the respective tumor-associated antigen. After the antibody-enzyme conjugate (Ab-E) has localized within the tumor and has been cleared from non-target sites, a prodrug, that is a substrate for the enzyme, is administered. Upon contact with the targeted enzyme, the prodrug is converted to the drug at the tumor site. This targeting approach has been well reviewed. An important dosing consideration with the ADEPT approach is optimizing the time interval between administration of the Ab-E and the prodrug. To attain adequate tumor uptake, high plasma and extracellular fluid levels of the Ab-E should typically be maintained for several hours 22, 23. Once adequate tumor levels are achieved (and prior to prodrug administration), sufficient time should be allowed for significant plasma clearance or inactivation of the non-tumor-associated AbE to minimize prodrug activation at non tumor sites (a potential source of toxicity).

CONCLUSION

The area of prodrug-mediated targeted drug delivery has made many strides within the last decade; however, there is still a great need for additional work to further improve existing approaches and to develop newer ones. At present prodrug are not prevalent in clinical use, in future there will be prodrugs for every known drug to make them effective in treatment. Drug discovery and prodrug development appear to be complementary for the generation of target specific medicines of future. The sole use of a prodrug to achieve targeted drug delivery is limited unless the target site possesses a unique enzyme system for activating the prodrug (as in the case of acyclovir). Hence, the combination of a prodrug approach with an additional approach which facilitates the targeting, as exemplified by the ADEPT. At present the research in this area is at a nascent stage due to lack of information, regarding all enzymes or receptors, most suitable for targeting purposes. As the unrevealing of the microbiological details of affected targets become clear, prodrug development will surely decrease side/toxic effect of drugs and also trigger development of more potent primary drugs.

 

 

 

 

 

 

 

References:

1. P K Banerjee and G L Amidon, Design of Prodrugs, (Ed.) H Bundgaard, New York: Elsevier; pp. 93-133, 1985. F M H de Groot, E W P Damen and H W Scheeren, Current Medicinal Chemistry 8, p.1093, 2001

. 2. Tripathi K.D. Essentials of medical pharmacology.4th edition , 25

3. IUPAC Pure and appl. chem., 1998, 70, 1129-1143.

4. Mayer D.L., Jungheim L.N, Law K.L., Mikolajczyle S.D.,Shapherd T.A., Cancer Res.,1993, sep.1:53(17):3956-63.

5. S.Kenneth, Prodrug topical and ocular drug delivery, 17- 22.

6. Kawakami S.,Yamishita.F., Hashida M., Adv. Drug Delivery Review,Vol 45,Issue 1, 6 dec 2000,77-88.

7. Meijer, D.K.F., Jansen, R.W. and Molema, G. (1992) Drug targeting systems for antiviral agents: options and limitations. Antiviral Res. 18, 215-258.

8. Wilding. I.R., Davis, S.S. and O?Hagan, D.T. (1994) Targeting of drugs and vaccines to the gut. Pharmacol. Ther. 62. 97-124.

 9. Tozer, T.N.. Friend, D.R. and McLeod, A.D. (1995) Kinetic perspectives on colonic delivery. STP Pharm. Sci. 5, S- 12.

 10. Friend, D.R. and Chang, G.W. (1985) Drug glycosides: potential prodrugs for colon-specific drug delivery. J.Med. Chem. 28, 51-57.

11. Simpkins, J.W., Smulkowski, M., Dixon, R. and Tuttle. R.E. (1988) Evidence for the delivery of narcotic antagonists to the colon as their glucuronide conjugates. J. Pharmacol. Exp. Ther. 244, 195-205.

12. Haeberlin. B., Rubas, W., Nolen, H.W. and Friend. D.R. (1993) In vitro evaluation of dexamethasone-P-oglucuronide for colon-specific drug delivery. Pharm. Res. 10 1553-1562.

13. Anwer, M.S., Kroker, R. and Hegner. D. (1976) Cholic acid uptake into isolated rat hepatocytes. Hoppe- Seyler?s Z. Physiol. Chem. 357 1477-1486.

14. Stephan, Z.F., Yurachek, E.C., Sharif, R., Wasvary. J.M.. Steele, R.E. and Howes, 80 International Journal of Current Research and Review www.ijcrr.com Vol. 03 issue 03 Mar 2011 C. (1992) Reduction of cardiovascular and thyroxine-suppressing activities of LT, by liver targeting with cholic acid. Biochem. Pharmacol. 43. 1969-1974.

15. Kramer, W., Wess, G.. Enhsen, A., Bock, K., Falk, E., Hoffman, A., Neckermann, G., Gantz, D., Schulz, S., Nickau, L.. Petzinger, E., Turley, S. and Dietschy, J.M. (1994) Bile acid derived HMG-CoA reductase inhibitors. Biochim. Biophys. Acta 1227, 137-154.

16. Neufeld, E. and Ashwell, G. (1979) Carbohydrate recognition systems for receptor-mediated pinocytosis. In: W. Lennarz (Ed.), Biochemistry of Glycoproteins and Proteoglycans, Plenum Press, New York, pp. 241-266.

17. Bodor and co-workers Bodor, N., Farag. H.H. and Brewster, M.E. (1981) Sitespecific, sustained release of drug to the brain. Science 214, 1370-1372.

18. Pop, E., Brewster, M.E. and Bodor, N. (1991) Sitespecific delivery of the central nervous system acting amines. Drugs Future 16, 919-944.

19. Kohler, H. and Milstein. C. (1975) Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature 256, 495. Waldmann, T.A. (1991) Monoclonal antibodies in diagnosis and therapy. Science 252, 1657-1662

20. Garnett, M.C., Embleton. M.J., Jacobs, E. and Baldwin, R.W. (1985) Studies on the mechanism of action of an anti-bodytargeted drug-carrier conjugate. AntiCancer Drug Des. 1. 3-12.

21. Deonarain, M.P. and Epenetos, A.A. (1994) Targeting enzymes for cancer therapy: old enzymes in new roles. Br. J. Cancer 70, 786-794.

22. Bagshawe, K.D., Sharma. SK., Springer, C.J. and Rogers. G.T. (1994) Antibody directed enzyme prodrug therapy (ADEPT). Ann. Oncol. 5, 879-891

. 23. Wallace, P.M. and Senter, P.D. (1994) Selective activation of anticancer prodrugs by monoclonal antibodyenzyme conjugates. Methods Find. Exp. Clin. Pharmacol. 16. 505-512.

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 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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