FORMULATION AND IN VIVO EVALUATION OF NANOEMULGEL-CONTAINING COCOA POD HUSK (THEOBROMA CACAO L.) EXTRACT AS TOPICAL ORAL PREPARATION

YANI CORVIANINDYA RAHAYU; ERNIE MADURATNA SETIAWATIE; RETNO PUDJI RAHAYU; BANUN KUSUMAWARDANI; NINIK MAS ULFA

doi:10.22159/ijap.2024v16i5.51294

Authors

YANI CORVIANINDYA RAHAYU Doctoral Study Program of Dental Science, Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia. Department of Oral Biology, Faculty of Dentistry, University of Jember, Jember, Indonesia https://orcid.org/0000-0002-9915-0468
ERNIE MADURATNA SETIAWATIE Department of Periodontology, Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia https://orcid.org/0000-0001-8262-974X
RETNO PUDJI RAHAYU Department of Oral Pathology and Maxillofacial, Faculty of Dental Medicine, Airlangga University, Surabaya, Indonesia
BANUN KUSUMAWARDANI Department of Biomedical Science, Faculty of Dentistry, University of Jember, Jember, Indonesia https://orcid.org/0000-0002-7296-7435
NINIK MAS ULFA Surabaya Pharmacy Academy, Surabaya, Indonesia https://orcid.org/0000-0003-0768-3548

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51294

Keywords:

Cocoa pod husk, Nanoemulgel, Topical oral preparation, Fibroblast, Collagen density

Abstract

Objective: Cocoa pod husk (Theobroma cacao L.) extract was applied to enhance bioavailability and drug effects due to antibacterial, antioxidant and anti-inflamation agents. Recent years have seen significant development of nanomedicine in non-invasive therapy of oral infection. The aim of this study was to develop the formula of nanoemulgel of Cocoa Pod Husk (CPH) extract for topical oral therapy compared its stability and evaluation in gingivitis rats with gels preparations on different gelling agents. Methods: The topical oral preparation were made in 4 formulations: F1 (CPH gel with gelling agent Sodium Carboxy Methyl Cellulose (Na-CMC) 3%); F2 (CPH gel with gelling agent Carbomer 1%); F3 (CPH nanoemulgel with gelling agent Na-CMC 3%); and F4 (CPH nanoemulgel with gelling agent Carbomer 1%. The physical characterization test of preparations were evaluated the pH, homogeneity, viscosity, spreadability and adhesion test. In vivo evaluation of gingivitis rats were observed using histological analysis of the fibroblast number and gingival collagen density in experimental Wistar rats by Hematoxylin eosin and Masson trichrome staining.Results: Four formulation (F1-F4) showed good stability in pH, viscosity, spreadability and adhesivity (p<0.05). The observation for 7 d after gel application to gingivitis rats, showed that the number of fibroblast and collagen density increasing in the treatment group compared to the control group (p<0.001). In the LSD test, F3 and F4 indicated the highest increase, however no significantly different (p>0.05).Conclusion: Nanoemulgel with Na-CMC as gelling agent potential to be used as an effective carrier for the active ingredients of CPH extract.

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References

Dhawan B, Aggarwal G, Harikumar S. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Investig. 2014;4(2):65-76. doi: 10.4103/2230-973X.133053, PMID 25006551.

Sindi AM, Hosny KM, Rizg WY, Sabei FY, Madkhali OA, Bakkari MA. Utilization of experimental design in the formulation and optimization of hyaluronic acid-based nanoemulgel loaded with a turmeric curry leaf oil nanoemulsion for gingivitis. Drug Deliv. 2023;30(1):2184311. doi: 10.1080/10717544.2023.2184311, PMID 36846914.

Mathew R, Varkey J. Formulation and in vitro evaluation of self nano emulsifying drug delivery system of quercetin for enhancement of oral bioavailability. Int J Curr Pharm Sci. 2022;14(1):60-9. doi: 10.22159/Ijcpr.2022v14i1.44113.

Aithal GC, Narayan R, Nayak UY. Nanoemulgel a promising phase in drug delivery. Curr Pharm Des. 2020;26(2):279-91. doi: 10.2174/1381612826666191226100241, PMID 31878849.

Hosny KM, Alhakamy NA, Sindi AM, Khallaf RA. Coconut oil nanoemulsion loaded with a statin hypolipidemic drug for management of burns formulation and in vivo evaluation. Pharmaceutics. 2020;12(11):1061. doi: 10.3390/pharmaceutics12111061, PMID 33171816.

Abdullah NA, Jufri M, Munim A, Saputri FC. Celastrol nanoemulgel formulation and in vitro penetration test. Int J Pharm Pharm Sci. 2020;12(8):82-91. doi: 10.22159/Ijpps.2020v12i8.37167.

Rahayu YC, Setiawatie EM, Rahayu RP, Ramadan DE. Analysis of antioxidant and antibacterial activity of cocoa pod husk extract (theobroma cacao l.). Dent J. 2023;56(4):220-5. doi: 10.20473/j.djmkg.v56.i4.p220-225.

Jalil AM, Ismail A. Polyphenols in cocoa and cocoa products is there a link between antioxidant properties and health. Molecules. 2008;13(9):2190-219. doi: 10.3390/molecules13092190, PMID 18830150.

Ackar D, Valek Lendic K, Valek M, Subaric D, Milicevic B, Babic J. Cocoa polyphenols can we consider cocoa and chocolate as potential functional food. Journal of Chemistry. 2013;2013(1)1-7. doi: 10.1155/2013/289392.

Choudhury H, Gorain B, Pandey M, Chatterjee LA, Sengupta P, Das A. Recent update on nanoemulgel as topical drug delivery system. J Pharm Sci. 2017;106(7):1736-51. doi: 10.1016/j.xphs.2017.03.042, PMID 28412398.

Algahtani MS, Ahmad MZ, Shaikh IA, Abdel Wahab BA, Nourein IH, Ahmad J. Thymoquinone loaded topical nanoemulgel for wound healing formulation design and in vivo evaluation. Molecules. 2021;26(13):3863. doi: 10.3390/molecules26133863, PMID 34202733.

Ismail SH, Hamdy A, Ismail TA, Mahboub HH, Mahmoud WH, Daoush WM. Synthesis and characterization of antibacterial Carbopol/Zno hybrid nanoparticles gel. Crystals. 2021;11(9):1092. doi: 10.3390/cryst11091092.

Rahayu YC, Setiawatie EM, Rahayu RP, Sakinah NN, Kusumawardani B, Gunadi A. Effects of cocoa pod husk extract (Theobroma cacao L.) on alveolar bone in experimental periodontitis rats. Trends Sci. 2023;20(6):6535. doi: 10.48048/tis.2023.6535.

Saryanti D, Setiawan I, Dayanto HH. Use of CMC Na as gelling agent in nanoemulgel formulation of methanol extract of sappan wood (Caesalpinia sappan L). J Trop Pharm Chem. 2022;6(1):21-9. doi: 10.25026/jtpc.v6i1.276.

Yadav VD, Shinde AD, Jadhav PD. Formulation and evaluation of liposomes containing fluconazole. Int J Drug Deliv Technol. 2022;12(1):98-102. doi: 10.25258/ijddt.12.1.19.

Patil A, Bhide S, Bookwala M, Soneta B, Shankar V, Almotairy A. Stability of organoleptic agents in pharmaceuticals and cosmetics. AAPS PharmSciTech. 2018;19(1):36-47. doi: 10.1208/s12249-017-0866-2, PMID 28900868.

Dwiastuti R, Bahar Gumilar KN, Yuliani H. Optimization and physical characterization of quercetin nanoemulgel formula as an antibacterial agent. Int J App Pharm. 2023;15(1):104-10. doi: 10.22159/Ijap.2023v15i1.46737.

Rognoni E, Pisco AO, Hiratsuka T, Sipila KH, Belmonte JM, Mobasseri SA. Fibroblast state switching orchestrates dermal maturation and wound healing. Mol Syst Biol. 2018;14(8):e8174. doi: 10.15252/msb.20178174, PMID 30158243.

Yusuf A, Almotairy AR, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems a review of the implication of nanoparticles physicochemical properties on responses in biological systems. Polymers (Basel). 2023;15(7):1596. doi: 10.3390/polym15071596, PMID 37050210.

Mahmoud EA, Bendas ER, Mohamed MI. Effect of formulation parameters on the preparation of superporous hydrogel self nanoemulsifying drug delivery system (SNEDDS) of carvedilol. AAPS PharmSciTech. 2010;11(1):221-5. doi: 10.1208/s12249-009-9359-2, PMID 20127427.

Ajazuddin, Alexander A, Khichariya A, Gupta S, Patel RJ, Giri TK. Recent expansions in an emergent novel drug delivery technology emulgel. J Control Release. 2013;171(2):122-32. doi: 10.1016/j.jconrel.2013.06.030, PMID 23831051.

Yoon BK, Jackman JA, Valle Gonzalez ER, Cho NJ. Antibacterial free fatty acids and monoglycerides biological activities experimental testing and therapeutic applications. Int J Mol Sci. 2018;19(4):1114. doi: 10.3390/ijms19041114, PMID 29642500.

Donthi MR, Munnangi SR, Krishna KV, Saha RN, Singhvi G, Dubey SK. Nanoemulgel a novel nano carrier as a tool for topical drug delivery. Pharmaceutics. 2023;15(1):164. doi: 10.3390/pharmaceutics15010164, PMID 36678794.

Jeengar MK, Rompicharla SV, Shrivastava S, Chella N, Shastri NR, Naidu VG. Emu oil based nano emulgel for topical delivery of curcumin. Int J Pharm. 2016;506(1-2):222-36. doi: 10.1016/j.ijpharm.2016.04.052, PMID 27109049.

Gohtani S, Prasert W. Nano emulsions emulsification using low energy methods. Japan J Food Eng. 2014;15(3):119-30. doi: 10.11301/jsfe.15.119.

El-Leithy ES, Makky AM, Khattab AM, Hussein DG. Nanoemulsion gel of nutraceutical co-enzyme q10 as an alternative to conventional topical delivery system to enhance skin permeability and anti-wrinkle efficiency. Int J Pharm Pharm Sci. 2017;9(10):207-1. doi: 10.22159/ijpps.2017v9i11.21751.

Bhattacharya S, Prajapati BG. Formulation and optimization of celecoxib nanoemulgel. Asian J Pharm Clin Res. 2017;10(8):353-65. doi: 10.22159/ajpcr.2017.v10i8.19510.

Rahmani SI, Zulkarnain AK. Optimization of HPMC and Na-CMC as gelling agents on physical properties and stability in sunflower seed oil gel formulation. J Food Pharm Sci. 2023;11(2):812-9. doi: 1146/jfps.82270.22.

Ullah N, Amin A, Farid A, Selim S, Rashid SA, Aziz MI. Development and evaluation of essential oil based nanoemulgel formulation for the treatment of oral bacterial infections. Gels. 2023;9(3):252. doi: 10.3390/gels9030252, PMID 36975701.

Taqwim Hidayat A, Thohar Arifin M, Nur M, Muniroh M, Susilaningsih N. Ozonated aloe vera oil effective increased the number of fibroblasts and collagen thickening in the healing response of full thickness skin defects. Int J Inflam. 2021 Feb 9;2021:6654343. doi: 10.1155/2021/6654343, PMID 33628417.

Schilrreff P, Alexiev U. Chronic inflammation in non healing skin wounds and promising natural bioactive compounds treatment. Int J Mol Sci. 2022;23(9):4928. doi: 10.3390/ijms23094928, PMID 35563319.

Abnaof K, Mallela N, Walenda G, Meurer SK, Sere K, Lin Q. TGF-β stimulation in human and murine cells reveals commonly affected biological processes and pathways at transcription level. BMC Syst Biol. 2014;8:55. doi: 10.1186/1752-0509-8-55, PMID 24886091.

Budi HS, Anitasari S, Ulfa NM, Juliastuti WS, Aljunaid M, Ramadan DE. Topical medicine potency of Musa paradisiaca var sapientum (L.) kuntze as oral gel for wound healing an in vitro in vivo study. Eur J Dent. 2022;16(4):848-55. doi: 10.1055/s-0041-1740226, PMID 35181871.

Ekeuku SO, Chin KY. Application of propolis in protecting skeletal and periodontal health a systematic review. Molecules. 2021;26(11):3156. doi: 10.3390/molecules26113156, PMID 34070497.

Morsy BM, El Domiaty S, Meheissen MA, Heikal LA, Meheissen MA, Aly NM. Omega-3 nanoemulgel in prevention of radiation induced oral mucositis and its associated effect on microbiome a randomized clinical trial. BMC Oral Health. 2023;23(1):612. doi: 10.1186/s12903-023-03276-5, PMID 37648997.