Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 623

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : December | Volume : 16 | Issue : 12 | Page : ZC01 - ZC06 Full Version

Formulation of In-situ Thermoreversible Gel with Moringa oleifera Lam Extract as a Local Drug Delivery System for Adjunct Periodontal Treatment


Published: December 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/58589.17206
Shanmuga Priya Ramamurthy, Priyadharshini Sekar, Arunmozhi Ulaganathan, Sheeja Varghese, Kadhiresan

1. Research Scholar, Department of Periodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. 2. Senior Lecturer, Department of Periodontics, Sri Venkateshwara Dental College and Hospital, The Tamil Nadu Dr. M.G.R Medical University, Chennai, Tamil Nadu, India. 3. Professor, Department of Periodontics, Sri Venkateshwara Dental College and Hospital, The Tamil Nadu Dr. M.G.R Medical University, Chennai, Tamil Nadu, India. 4. Professor, Department of Periodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India. 5. Professor, Department of Periodontics, Sri Venkateshwara Dental College and Hospital, The Tamil Nadu Dr. M.G.R Medical University, Chennai, Tamil Nadu, India.

Correspondence Address :
Dr. Shanmuga Priya Ramamurthy,
Research Scholar, Department of Periodontics, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences,
Chennai-600077, Tamil Nadu, India.
E-mail: drshanpriya@gmail.com

Abstract

Introduction: Periodontal disease is an outcome of a plethora of molecular mechanisms associated with oxidative stress, inflammation and oral microorganisms is managed by surgical or non surgical therapies with systemic antibiotics. However, local drug delivery system is known to augment the currently available therapies and improves prognosis. Although, there are several local drug delivery systems available, the search for an ideal agent with antioxidant, antimicrobial and anti-inflammatory properties continues. Moringa oleifera Lam extracts is one such wonder plant with all the above mentioned effects.

Aim: To formulate an in-situ thermoreversible gel with Moringa oleifera Lam extract that could be used as a local drug delivery system as an adjunct to periodontal treatment.

Materials and Methods: This in-vitro study was conducted in Nanotechnology Laboratory, Department of Pharmacology at Saveetha Dental College, from May 2022 to June 2022. For preparation of thermoreversible gel the 19% of thermogelling polymer poloxamer 407 (15% to 30%w/v) which the least concentration that demonstrates thermoreverisibility at 36°C and 0.2% which is the least concentration of mucoadhesive polymer carbapol 934 (0.2% to 0.5% w/v) which forms sol-gel transition and 5% aqueous extract of Moringa oleifera and cold deionised water were used. Surface pH, gelation temperature, syringeability, in-vitro drug release, stability, gelation time and Fourier Transform Infrared Spectroscopy (FTIR) analysis was done.

Results: The surface pH of the gel was 6.94±0.091 with a gelation temperature of 34°C±0.5. The gel was flowable with good stability and fast release of eight hours. The chemical components compatability study of Moringa oleifera Lam powder, thermoreversible gel without extract and thermoreversible gel with extract were subjected to FITR analysis. The spectral analysis showed no significant chemical interaction between the Moringa oleifera and thermoreversible gel.

Conclusion: The study concluded that the thermoreversible gel with Moringa oleifera Lam extracts could be used as an adjunct for the management of periodontal disease with good bioavailability. However, future clinical studies have to be conducted to validate the results of the present study.

Keywords

Antioxidant, Anti-inflammatory, Drug release, In-vitro, Local delivery, Periodontitis

Chronic periodontitis results in tissue destruction caused by gram negative microorganisms in periodontal pocket and resultant inflammation [1-3]. The principal aim of periodontal treatment is to eliminate the microorganisms and thereby, ceasing disease progression. The use of systemic antibiotics along with non surgical therapy is not very effective alternative, as it holds many drawbacks. Those are, the required concentration of the antimicrobial agent is not maintained in the gingival crevicular fluid after first pass metabolism, undesirable gastrointestinal side effects, since, it does not have a targeted effect and poor patient compliance (4). Local drug delivery system can be more effective in reducing the periodontal pocket microbial load as it can have a direct effect on the locally invaded pathogens. Hence, drugs like chlorhexidine, metronidazole, doxycycline were incorporated for local release in non surgical management of periodontitis. However, the biggest challenge is sustained release of the drug against the constant flushing action of oral fluids like Gingival Crevicular Fluid (GCF) and saliva (5). This could be overcome by the type of vehicle used for drug delivery. Polymers are promising for sustained release of the drug. Local drug delivery for intra pocket administration is delivered as fibres, strips, gels, chip, micro/nano particle and liposomes. Among them, gels easily flows through the delivery device and can reach all over the pocket. It has a faster drug release at the same time it is bioadhesive. These advantages make gels a viable option for sustained local drug delivery in periodontal therapy (6).

Recently, there has been more interest in exploring the antimicrobial properties of herbs and plant derived products. The advantages of using plants and plant derived products is that they also possess antioxidant and anti-inflammatory properties, that can aid in the management of periodontal disease as the disease is associated with both inflammation and oxidative stress. In this regard, Moringa oleifera Lam, a plant of Indian origin termed as drumstick has received attention due to the various phototherapeutic effects. It is currently used as a nutraceutical agent in African countries (7),(8).

This wonder herb has various phytochemical constituents such as polyphenols, flavonoids, alkaloids, carotenoids, vitamins, saponins, phenolic acids, isothiocyanates, glucosinolates and tannins (9). It has been used for the management of infectious diseases such as typhoid and malaria as well as systemic diseases like diabetes and hypertension (10),(11). Among the oral diseases, the effect of Moringa oleifera Lam had been studied on oral biofilms, for management of oral thrush and were incorporated in toothpaste to study its anticaries effect (12). For its effect on periodontitis, there was a reduction in proinflammatory cytokines Tumour Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β) in a study conducted on rats periodontitis model (13). Similarly, Moringa oleifera Lam extract showed an antiperiodontitis effect by inhibiting alveolar bone resorption by its action on p38α MAPK pathway in experimental periondontitis (14). In addition, the antioxidant and anti-inflammatory properties of the plant have also been previously reported in many studies (15),(16),(17).

The thermoreversible gel is made of a biopolymer that changes from sol to a gel form with change in temperature. The sol form of the drug at room temperature gelates at pocket temperature and thus can release the drug for prolonged duration. This makes it an ideal one to locally manage periodontal diseases due to better bioavailability of the drug (18). Hence, aim of the present study was to formulate an in-situ thermoreversible gel with Moringa oleifera Lam extract that can be used as a local drug delivery system as an adjunct to periodontal treatment.

Material and Methods

This in-vitro study was conducted in Nanotechnology Laboratory, Department of Pharmacology at Saveetha Dental College, from May 2022 to June 2022. The approval was obtained from the Ethics Committee of Saveetha Dental College (SDC/Ph.D18/32). The polymers Carbapol 934 and Poloxmer 407 were procured from Sigma Aldrich, Mumbai. The 5% aqueous Moringa oleifera extract was prepared based on previous study results on its antioxidant and anti-inflammatory property (19).

Formulation of Thermoreversible Gel

For preparation of thermoreversible gel the 19% of thermogelling polymer poloxamer 407 and 0.2% mucoadhesive polymer Carbapol 934 were selected. This concentration demonstrated thermoreversibility of sol-gel transition at 36°C as observed in thermoreversible gel optimisation studies for local drug delivery in periodontal pockets. And it is the least concentration to produce the effect (20),(21),(22). To this, 5% aqueous extract of moringa oleifera and cold deionised water were added. To prepare 50 mL of gel, 2.5 mL of 5% extract was added to 9.25 gm of poloxamer dissolved in 40 mL of water, 0.75 gm carbapol dissolved in 10 mL of water and mixed (20). Sols were prepared on weight basis using the cold method (21). Poloxamer 407 was slowly added to cold water (4-5°C) and constant stirring was maintained (Table/Fig 1). The dispersion was refrigerated until a clear solution was obtained (4-5 hours). To the solution, Carbapol 934 was added in a concentration of 0.2% and mixed thoroughly. Further, Moringa oleifera extract was combined and the gel prepared (Table/Fig 2),(Table/Fig 3).

Surface pH: The surface pH of the prepared in-situ gel was measured with a digital laboratory pH meter, equilibrated for 1 min.

Gelation temperature: A total of 5 mL sol was taken in test tubes and sealed with aluminum foil. This was placed in thermostat controlled electric water bath at 4°C. Slowly the water bath temperature was increased by 1°C to allow equilibration of the sol for 60 seconds at every degree of temperature rise. Frequent examination for completion of gelation was observed. When the meniscus was static upon tilting the test tube at 90°, showed completion of gelation (21).

Gelation time: Gelation time was determined under motion condition using a magnetic stirrer. The sol with magnetic stirrer (IKA, Germany) at hundred revolutions per minute was done. The time taken for the magnetic bead to become static was calculated as the gelation time and the experiments were done in triplicate (23).

Syringeability: A 1 mL of the formulated gel was loaded into a syringe of 5 mL capacity with 21 gauge needle. The test was considered positive, if the gel was disseminated through the syringe.

Fourier Transform Infrared Spectroscopy (FTIS): The chemical components interaction between Moringa oleifera and polaxamer was analysed by attenuated total reflectance-FTIR (Bruker Alpha II FTIR) in the spectral region of 4000-400 cm-1 wavelength with 4 cm-1 resolution at total scans of 32. The test samples Moringa oleifera powder, plain thermoreversible gel and thermoreversible gel with extract were made into pellets and investigated. The IR spectroscopy provides with a quantitative output analysis depending upon the proportion of infrared absorption of the chemical components. This helps in identifying the functional groups (24).

In-vitro drug release: The targeted location of the prepared thermoreversible Moringa gel is periodontal pocket. It is a confined space bathed by continuous Gingival Crevicular Fluid (GCF) flow of pH between 6.8 to 7.4 (21). Since, the flow of GCF could not be represented in-vitro, a static dissolution model was adopted. In this model, the phosphate buffer of pH 7.2 represented the dissolution medium similar to gingival fluid and the amount of drug release into the medium was assessed spectrophotometrically at fixed time intervals (25). The procedure involves to 5 mL of the buffer taken in a test tube, 1 mL of the prepared formulation was laid and temperature of the buffer was maintained at 37±1°C similar to periodontal pocket temperature (26). On completion of the scheduled specific time interval (1, 2, 3, 4, 8 and 12 hourly) spectrophotometric analysis of 1 mL of the sample taken from the medium was done at 261.5 nm. Replacement of the buffer with new buffer medium was done after analysis (21).

Stability test: The prepared gel was assessed for its stability during storage at a refrigerator temperature between 2 to 50 c. At a time interval of 7, 15 and 30 days, a sample of the formulation for subjected to spectrometric analysis.

Palatability: It is the test used to assess the acceptance of the preparation by one’s mind. The test was conducted between the age group of 24-35 years among six volunteers. The sample size was calculated according to study by Kumari N and Pathak K (27). A 5 mL of the formulated gel was given and advised to swish and spit after one minute The taste perceived at the end were recorded on a VAS score.

Statistical Analysis

The data was analysed and presented as in tabular and graph form.

Results

The surface pH was found to be 6.94±0.091 and gelation temperature was the gel converted from sol to gel form at 34±0.5°C. The gelation time (time taken for gelation) was 1 min 20 seconds for conversion from sol state to gel. The syringeability-formulation had passed the test, as it had flowed easily. The FTIR analysis graph (Table/Fig 4) was assessed for the peaks and patterns and comparisons were made between the Moringa oleifera powder, plain thermoreversible gel and thermoreversible gel with extract. The absorption peaks were noted at 2918.82 cm-1 (strong, broad O-H stretching signifying carboxylic acid), 2850.39 cm-1 (medium C-H stretching alkane) and 2352.37 cm-1 (strong O=C=O, carbondioxide) for Moringa oleifera. The IR spectrum of plain thermoreversible gel showed principal peaks at 3345.51 (strong, N-H stretch), 2108.37 (variable C=C stretch), 1636.39 cm-1 (weak C=C alkene), 1300.20 cm-1 (strong NO2 stretch) and strong C-F bond at 1254.46 cm-1. The thermoreversible gel with extract showed functional peaks at 3345.64 (strong, N-H stretch, secondary amine), 2364.37 cm-1 (strong O=C=O,carbondioxide), 2105.37 (variable C=C stretch), 1640.23 cm-1 (strong C=C stretching alkene), 1297.83 cm-1 (strong strong C-N stretching, aromatic amine) and strong C-O stretching alkyl aryl ether at 1254.47 cm-1. The spectrum results indicated that the physical mixture of Moringa oleifera and thermoreversible gel has not shown any interactions among their components (Table/Fig 2).

In-vitro drug release revealed a steady increase from 1 hour (29.35%) to 8 hours and reaching a maximum of 98.60% and a slight decrease at 12 hours of 96.21%. the results are depicted in (Table/Fig 5),(Table/Fig 6). Palatability- taste perceived by the six volunteers were recorded on the VAS 0 to 10 is presented in (Table/Fig 7). Mean score observed was 5.16±0.75. 16.66% commented to be poor, 33.3% felt it to be good, and 50% of volunteers recorded it as neither good or bad. In stability tests, the drug was found to be stable up to one month with a drug content of 99.54% when prepared fresh, 99% at one week, 98.57% at 15 days and 98.32% at one month (Table/Fig 8).

Discussion

The use of antimicrobial and anti-inflammatory agents as an adjunct to periodontal therapy reduces microbial load and inflammation thereby preventing further destruction of periodontal tissues. However, the use of systemic medications is associated with the major limitation of bioavailability in the gingival crevicular fluid that is in close proximity to the periodontal pocket (3). Hence, recently Local Drug Delivery (LDD) system is used currently due to the sustained release and bioavailability. For administration of drugs through LDD in periodontal pockets, thermoreversible gel which converts from one form to the other with change in temperature is ideal to maintain the adequate concentration of the drug in periodontal pockets (25).

Although several synthetic molecules such as chlorhexidine, metronidazole, doxycycline are in use, the search for herbal and plant derived products for the management of periodontal disease continues (22),(27),(28),(29). The use of plant-derived products have several advantages such as ease of availability, diverse phyto therapeutic properties due to a mixture of active ingredients, less likely to have side effects being diet derived (30). In this regard, in the present study, aqueous Moringa oleifera Lam extracts was chosen due to the fact that it is indigenous to India hence easily available and have several phytochemicals that exert antioxidant, antimicrobial and anti-inflammatory properties to formulate a thermoreversible gel (8).

The main aim of the developing LDD is maintenance of the adequate concentration of the drug at the required site for required duration. In this regard, sustained drug release system maintains the required concentration for a day and controlled release system maintain the concentration of the drug for more than 24 hours (31),(32). Recently the use of biodegradable polymers with thermoreversible property has gained importance as the sol converts into gel form when injected into the periodontal pocket, thereby, providing sustained release (33). In the present study, the authors used thermos gelling polymer, poloxamer 407 and a mucoadhesive polymer carbopol 934 for formulation of in-situ gel of Moringa oleifera by cold method. Similarly, in a study by Balakrishnan P et al., they have used poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer for intranasal drug delivery to improve the solubility and increased absorotion of for Fexofenadine Hydrochloride (FXD HCl) (34). Similarly, in a narrative review Chen Y et al., have reported the advantages of using Poloxamer 407 for oral formulation that improves the bioavailability of the drug (35).

In the present study, a formulation with the extract was done for direct placement into the periodontal pocket, where the sol form would undergo gelation at periodontal pocket temperarture and pH. Usually the ideal gelation temperature for periodontal gels is 35°C to 37°C. For instance, if the gelation temperature is below 25°C, a gelation could occur at room temperature and hence manufacturing, handling administering and shelf-life could be difficult. If the gelation temperature is greater than 37°C, the gelation would not occur in the oral cavity and hence, bioavailability of the drug would be reduced (33).

The FTIR spectroscopy assessment revealed that the formulated gel with Moringa oleifera Lam extract did not undergo changes in chemical composition thereby the functional groups remained unaltered in the prepared gel. The surface pH of the gel was 6.94±0.091 with a gelation temperature of 34±0.5°C. As the temperature of the periodontal pocket ranges between 36°C, and 37°C, authors used the poloxamer 407 and carbopol 934 that may gel below 36°C.

It is a well known fact that there is a reduction in gelation temperature with an increase in concentration of P407 (30). Hence we chose 19% of thermogelling polymer Poloxamer 407 (16) (15% to 30% w/v) which the least concentration that demonstrates thermoreverisibility at 36°C and 0.2% which is the least concentration of mucoadhesive polymer Carbapol 934 (0.2% to 0.5% w/v) forms sol-gel transition. The pH was also well within the range of the absorption site. The gel was palatable and flowable with good stability with a 99.54% drug in freshly prepared formulation with the slight decrease over a period of time and was found to be 98.32% at one month. However long-term stability studies have to be carried out. The gelation time was 1 minute 20 seconds, which is well within the required range. Considering the release there was a time-dependent increase in drug release from one hour to eight hours and a slight decrease after 12 hours which is adequate for periodontal therapy. The FTIR analysis revealed that Moringa oleifera Lam extract was pure and could be used for further study.

Many research works were performed in the formulation of appropriate thermoreversible gel for periodontal pocket delivery. Various antibiotics, host modulating agents and phytochemicals have been tried (20),(21),(22),(27),(28),(29). There were two reported clinical trials (36),(27), in one, adjunctive local drug therapy with thermo-reversible green tea gel has been shown to reduce periodontal pocket depth and inflammation when compared to scaling and rootplaning during the four weeks of the clinical trial in patients with chronic periodontitis. The results are attributed to both antimicrobial and anti-inflammatory activity of green tea catechin (36).

In the other clinical study, the effect of combination of levofloxacin, metronidazole with chitosan and poloxamer 407 on clinical signs of periodontal inflammation was determined. Though, there was gain in clinical attachment level and reduction of gingival signs of inflammation, the sample size was too small to conclude on the results (27).

In one of the studies, formulation of thermoreversible gel using simvastatin was researched. In that study, 2.2% simvastatin was used against various concentrations of Poloxamer 407 and methyl cellulose. And the study concluded, 25% Poloxamer and 5% MC was successful combination to show an in-vitro drug release for six days (37). But, in the present study authors had used Carbapol in place of methylcelluslose since, its proved that for intraoral usage carbapol in combination with poloxamer showed better bioadhesiveness (38).

In yet another study, temperature sensitive intrapocket gel preparation was done with 0.1% w/v chlorhexidene using Poloxamer 407, Poloxamer 188 and carbapol. And among different concentrations Poloxamer 407 in 19% with 0.2% carbapol had the highest desirable outcome for intrapocket delivery. Accordingly in the present study, the observed concentration was adopted to prepare the thermoreversible gel (22).

Many more studies have been conducted with cephalexin (21), metronidazole with serratiopeptidase (27), doxycycline with and without lipoxin (29) and moxifloxacin hydrochloride (20) in the preparation of thermoreversible injecteable gels for local drug delivery of these active agents for the management of periodontitis. Some studies have been listed in (Table/Fig 9) (5),(20),(21),(22),(27),(28),(36),(37).

However, only one study using herb-like green tea was studied and observed to be efficient clinically among patients with periodontitis (21). The present thermoreversible gel formulated with 5% Moringa oleifera Lam extract with adequately investigated. And the present study is the first of its kind to use Moringa oleifera Lam extract in thermoreversible gel form for oral usage. It was observed to have adequate retentive characteristics and suitable sol gel transition for intrapocket delivery.

Limitation(s)

The limitation of the study includes that the antioxidant, anti-inflammatory and antimicrobial properties of the gel, have not been assessed. In future, the toxicity studies and evaluation of clinical benefits of thermoreversible in-situ Moringa oleifera Lam gel in the treatment of periodontitis should be assessed by well-designed randomised controlled or clinical trial.

Conclusion

The prepared in-situ thermoreversible gel with the active agent 5% Moringa oleifera Lam extract, hydrogels like Poloxamer 407 (19%) and Carbapol 0.2% established a favourable rheological outcomes much suitable for intaoral pocket delivery. There was a sustained drug release which declined slowly only after 12 hours of activity. In the prepared gel, sol-gel temperature shift was observed to happen at 34±0.5°C which was more comparable with intra oral temperature. This Moringa oleifera Lam extract thermosensitive gel has the required properties for local drug delivery in periodontal pocket and could be explored as an adjunct in periodontal treatment, thereby, improving the prognosis of the disease.

References

1.
Greenstein G, Polson A. The role of local drug delivery in the management of periodontal diseases: A comprehensive review. J Periodontol. 1998;69(5):507-20. [crossref] [PubMed]
2.
Yuvaraja M, Reddy NR, Kumar PM, Ravi K, Alqahtani N. Thermoreversible gel for intrapocket delivery of green tea catechin as a local drug delivery system: An original research. J Adv Pharm Technol Res. 2016;7(4):139-43. [crossref] [PubMed]
3.
Pasupuleti MK, Nagireddy RR, Dinahalli R, Anumala D, Kishore Kumar A, Chavan V. Microbiological tests to identify a link between periodontitis and acute myocardial infarction-an original research. Iran J Microbiol. 2013;5(4):391-95.
4.
Pragati S, Ashok S, Kuldeep S. Recent advances in periodontal drug delivery systems. Int J Drug Deliv. 2009;1(1):01-14. [crossref]
5.
Jones SD, Woolfson DA, Brown FA, Michael J, Neill O. Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to periodontal pocket. In vitro release kinetics, syringeability, mechanical and and mucoadhesive properties. J Contr Rel. 2002;49(1):71-79. [crossref]
6.
Jain N, Gaurav K, Javed S, Iqbal Z, Talegaokar S, Ahmad FJ, et al. Recent approaches for the treatment of periodontitis. Drug Discov Today. 2008;13 (21-22): 932-43. [crossref] [PubMed]
7.
Escobar-Chávez JJ, López-Cervantes M, Naïk A, Kalia YN, Quintanar-Guerrero D, Ganem-Quintanar A. Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. J Pharm Pharm Sci. 2006;9(3):339-58.
8.
Kasolo, JN, Bimenya GS, Ojok L, Ochieng J, Ogwal-Okeng JW. Phytochemicals and uses of Moringaoleifera leaves in Ugandan rural communities. J Med Plants Res. 2010;4:753-57.
9.
Gupta S, Jain R, Kachhwaha S, Kothari SL. Nutritional and medicinal applications of Moringa oleifera Lam. Review of current status and future possibilities. J Herb Med. 2018;11:01-11. [crossref]
10.
Leone A, Spada A, Battezzati A, Schiraldi A, Aristil J, Bertoli S. Cultivation, genetic, ethnopharmacology, phytochemistry and pharmacology of moringa oleifera leaves: An overview. Int J Mol Sci. 2015;16(12):12791-35. [crossref] [PubMed]
11.
Sivasankari B, Anandharaj M, Gunasekaran P. An ethnobotanical study of indigenous knowledge on medicinal plants used by the village peoples of Thoppampatti, Dindigul district, Tamilnadu, India. J Ethnopharmacol. 2014;153(2):408-23. [crossref] [PubMed]
12.
Nurul M, Muhammad Harun. Systematic review of moringa oleifera’s potential as antibacterial and anti-inflammatory in the oral cavity. European Journal of Molecular & Clinical Medicine. 2020;7(10):144-61.
13.
Sugiharto S, Ramadany S, Handayani H, Achmad H, Mutmainnah N, Inayah NH, et al. Assessment of the anti-inflammatory activities of the moringa leaf extract in periodontitis cases through IL-6 cytokine analysis in wistar (rattus novergicus). Open Access Maced J Med Sci. 2022;10(D):124-30. [crossref]
14.
Wang F, Long S, Zhang J. Moringa oleifera Lam. Leaf extract safely inhibits periodontitis by regulating the expression of p38α/MAPK14-OPG/RANKL. Arch Oral Biol. 2021;132:105280. [crossref] [PubMed]
15.
Xu YB, Chen GL, Guo MQ. Antioxidant and anti-inflammatory activities of the crude extracts of moringa oleifera from Kenya and their correlations with flavonoids. Antioxidants. 2019;8(8):296. [crossref] [PubMed]
16.
Atawodi SE, Atawodi JC, Idakwo GA, Pfundstein B, Haubner R, Wurtele G, et al. Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of moringa oleifera Lam. J Med Food. 2010;13(3):710-16. [crossref] [PubMed]
17.
Siddhuraju P, Becker K. Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves. J Agric Food Chem. 2003;51(8):2144-55. [crossref] [PubMed]
18.
Borchard W. Properties of thermoreversible gels. Berichte der Bunsengesellschaft für Phys Chemie. 1998;102(11):1580-88. [crossref]
19.
Ramamurthy S, Thiagarajan K, Varghese S, Kumar R, Karthick BP, Varadarajan S, et al. Assessing the in vitro antioxidant and anti-inflammatory activity of moringa oleifera crude extract. J Contemp Dent Pract. 2022;23(4):437-42. [crossref] [PubMed]
20.
Swain GP, Patel S, Gandhi J, Shah P. Development of moxifloxacin hydrochloride loaded in-situ gel for the treatment of periodontitis: In-vitro drug release study and antibacterial activity. J Oral Biol Craniofac Res. 2019;9(3):190-200. [crossref] [PubMed]
21.
Parvathy S, Unnikrishnan A, George OP, Nair SC. Thermoreversible-pH sensitive cephalexin insitu gel for treating periodontal disease. J Chem Pharm Res. 2015;7(5):555-67.
22.
Garala K, Joshi P, Shah M, Ramkishan A, Patel J. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig. 2013;3(1):29-41. [crossref] [PubMed]
23.
Dang-liang Wang, Han-ying Bai, Gao Yue. Gel Characteristics of urea-formaldehyde resin under shear flow conditions. Mathematical Problems in Engineering. 2013;2013:01-05. [crossref]
24.
George TT, Oyenihi AB, Rautenbach F, Obilana AO. Characterization of moringa oleifera leaf powder extract encapsulated in maltodextrin and/or gum arabic coatings. Foods. 2021;10(12):3044. [crossref] [PubMed]
25.
Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RSR. Thermoreversible- mucoadhesive Gel for nasal delivery of sumatriptan. AAPS Pharm Sci Tech. 2006;7(3):E80-E86. [crossref] [PubMed]
26.
Mukherjee S. The temperature of the periodontal pockets. J Clin Periodontol. 1981;8(1):17-20. [crossref] [PubMed]
27.
Kumari N, Pathak K. Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: Statistical optimization and mechanistic evaluation. Curr Drug Deliv. 2012;9(1):74-84. [crossref] [PubMed]
28.
Bansal M, Mittal N, Yadav SK, Khan G, Mishra B, Nath G. Clinical evaluation of thermoresponsive and mucoadhesive chitosanin situ gel containing Levofloxacin and Metronidazole in the treatment of periodontal pockets-A split-mouth, clinical study. J Pierre Fauchard Acad (India Sect). 2016;30(1):06-14. [crossref]
29.
Wang B, Booij-Vrieling HE, Bronkhorst EM, Shao J, Kouwer PHJ, Jansen JA, et al. Antimicrobial and anti-inflammatory thermo-reversible hydrogel for periodontal delivery. Acta Biomater. 2020;16:259-67. [crossref] [PubMed]
30.
Ramamurthy S, Varghese S, Sudarsan S, Muruganandhan J, Mushtaq S, Patil PB, et al. Moringa oleifera: Antioxidant, anticancer, anti-inflammatory, and related properties of extracts in cell lines: A review of medicinal effects, phytochemistry, and applications. J Contemp Dent Pract. 2021;22(12):1483-92. [crossref]
31.
Addy M, Rawle L, Handley R, Newman HN, Coventry JF. The development and in vitro evaluation of acrylic strips and dialysis tubing for local drug delivery. J Periodontol. 1982;53(11):693-99. [crossref] [PubMed]
32.
Jenabian N, Moghadamnia AA, Karami E, Mir APB. The effect of Camellia Sinensis (green tea) mouthwash on plaque-induced gingivitis: A single-blinded randomized controlled clinical trial. DARU J Pharm Sci. 2012;20(1):39. [crossref] [PubMed]
33.
Yadav R, Kanwar IL, Haider T, Pandey V, Gour V, Soni V. In situ gel drug delivery system for periodontitis: An insight review. Futur J Pharm Sci. 2020;6:33-37. [crossref]
34.
Balakrishnan P, Park EK, Song CK, Ko HJ, Hahn TW, Song KW, et al. Carbopol- incorporated thermoreversible gel for intranasal drug delivery. Molecules. 2015;20(3):4124-35. [crossref] [PubMed]
35.
Chen Y, Lee JH, Meng M, Cui N, Dai CY, Jia Q, et al. An overview on thermosensitive oral gel based on poloxamer 407. Materials (Basel). 2021;14(16):4522-25. [crossref] [PubMed]
36.
Chava VK, Vedula BD. Thermo-reversible green tea catechin gel for local application in chronic periodontitis: A 4-week clinical trial. J Periodontol. 2013;84(9):1290-96. [crossref] [PubMed]
37.
Rajendran S, Kumar KS, Ramesh S, Rao SR. Thermoreversible in situ gel for subgingival delivery of simvastatin for treatment of periodontal disease. Int J Pharm Investig. 2017;7(2):101-06. [crossref] [PubMed]
38.
Shin SC, Kim JY, Oh IJ. Mucoadhesive and physicochemical characterization of Carbopol-Poloxamer gels containing triamcinolone acetonide. Drug Dev Ind Pharm. 2000;26(3):307-12. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/58589.17206

Date of Submission: Jun 21, 2022
Date of Peer Review: Aug 20, 2022
Date of Acceptance: Oct 18, 2022
Date of Publishing: Dec 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jun 23, 2022
• Manual Googling: Oct 10, 2022
• iThenticate Software: Oct 17, 2022 (4%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com