Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone
DOI:
https://doi.org/10.1590/s2175-97902022e20041%20Keywords:
Dexamethasone, Gellan gum, Mucoadhesive gel, Oral precancerous lesions, Cell cultureAbstract
This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.
Downloads
References
Afewerki S, Sheikhi A, Kannan S, Ahadian S, Khademhosseini A. Gelatin-polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics. Bioeng Transl Med. 2019;4(1):96-115.
Amasya G, Karavana SY, Şen T, Baloğlu E, Tarımcı N. Bioadhesive and mechanical properties of triamcinolone acetonide buccal gels. Turk J Pharm Sci. 2012;9(1):1-12.
Andrews GP, Gorman SP, Jones DS. Rheological characterisation of primary and binary interactive bioadhesive gels composed of cellulose derivatives designed as ophthalmic viscosurgical devices. Biomaterials. 2005;26(5):571-580.
Andrews GP, Jones DS. Rheological characterization of bioadhesive binary polymeric systems designed as platforms for drug delivery implants. Biomacromolecules. 2006;7(3):899-906.
Ayushee Hebbale M, Mhapuskar A, Agarwal R. Orotransmucosal drug delivery system: A forgotten hero. J Adv Med Dent Scie Res. 2017;5(7):32-38.
Baloglu E, Karavana SY, Ay Senyigit Z, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Tech. 2011;16(6):627-636.
Butoescu N, Jordan O, Petri-Fink A, Hofmann H, Doelker E. Co-encapsulation of dexamethasone 21-acetate and SPIONs into biodegradable polymeric microparticles designed for intra-articular delivery. J Microencapsul. 2008;25(5):339-350.
Cancer facts and figures 2002, National Home Office: American Cancer Society, Inc., Atlanta, GA 30329-4251.
Cevher E, Taha MAM, Orlu M, Araman A. Evaluation of mechanical and mucoadhesive properties of clomiphene citrate gel formulations containing carbomers and their thiolated derivatives. Drug Deliv. 2008;15(1):57-67.
Chang JY, Oh YK, Choi H, Kim YB, Kim CK. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm. 2002a;241(1):155-163.
Chang JY, Oh YK, Kong HS, Kim EJ, Jang DD, Nam KT, et al. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J Control Release. 2002b;82(1):39-50.
Chinna Reddy P, Chaitanya KSC, Madhusudan Rao Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. DARU J Pharm Sci. 2011;19(6):385-403.
Chole RH, Patil R. Drug treatment of oral sub mucous Fibrosis-A review. Int J Contemp Med Res. 2016;3(4):996-998.
Dabhi MR, Nagori SA, Gohel MC, Parikh RK, Sheth NR. Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design. Drug Deliv. 2010;17(7):520-531.
Desai UH, Patwari AH, Maradiya JK, Sathawara MK, Suhagia BN, Rathod IS. RP-HPLC method for simultaneous estimation of ciprofloxacin and dexamethasone in eye/ear drops. Int J Pharm Sci Res. 2013;5(2):62-66.
Fernandez M, Von Plessing C, Cardenas G. Preparation and characterization of chitosan gels. J Chil Chi Soc. 2006;51(4):1022-1024.
Friedrich RB, Camponogara Fontana M, Beck RCR, Raffin Pohlmann A, Stanisçuaski Guterres S. Development and physicochemical characterization of dexamethasone-loaded polymeric nanocapsule suspensions. Quim Nova. 2008;31(5):1131-1136.
Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, et al. Tobacco smoking and cancer: a meta-analysis. Int J Cancer. 2008;122(1):155-64.
Goldstein BY, Chang SC, Hashibe M, La Vecchia C, Zhang ZF. Alcohol consumption and cancers of the oral cavity and pharynx from 1988 to 2009: an update. Eur J Cancer Prev. 2010;19(6):431-65.
Gousia Begum S, Sekar M. Formulation and evaluation of tinidazole mucoadhesive buccal gels. Int J Pharm Bio Sci. 2017;8(2):48-55.
Goyall R, Tripathi SK, Tyagi S, Ravi Ram K, Ansari KM, Shukla Y, et al. Gellan gum blended PEI nanocomposites as gene delivery agents: Evidences from in vitro and in vivo studies. Eur J Pharm Biopharm. 2011;79(1):3-14.
Guan Q, Sun D, Zhang G, Sun C, Wang M, Ji D, et al. Docetaxel-loaded self-assembly stearic acid-modified bletilla striata polysaccharide micelles and their anticancer effect: Preparation, characterization, cellular uptake and in vitro evaluation. Molecules. 2016;21(12):E1641.
Gupta H, Aqil M, Khar RK, Ali A, Bhatnagar A, Mittal G. An alternative in situ gel-formulation of levofloxacin eye drops for prolong ocular retention. J Pharm Bioallied Sci. 2015;7(1):9-14.
Hambly JL, Haywood A, Hattingh L, Nair RG. Comparison between self-formulation and compounded formulation dexamethasone mouth rinse for oral lichen planus: A pilot randomized cross-over trial. J Investig Clin Dent. 2017;8(3).
Harish NM, Prabhu P, Charyulu RN, Gulzar MA, Subrahmanyam EVS. Formulation and evaluation of in situ gels containing clotrimazole for oral candidiasis. Indian J Pharm Sci. 2009;71(4):421-427.
Hazzah HA, Farid RM, Nasra MMA, Zakaria M, Gawish Y, El-Massik MA, et al. Fullerene-C60-modified edge plane pyrolytic graphite electrode for the determination of dexamethasone in pharmaceutical formulations and human biological fluids. Biosens Bioelectron. 2009;24(6):1649-1654.
Hopkins RL, Leinung MC. Exogenous Cushing’s syndrome and glucocorticoid withdrawal. Endocrinol Metab Clin North Am. 2005;34(2):371-84.
Imam SS, Aqil M, Akhtar M, Sultana Y, Ali A. Formulation by design-based proniosome for accentuated transdermal delivery of risperidone: in vitro characterization and in vivo pharmacokinetic study. Drug Deliv. 2015;22(8):1059-1070.
James L, Shetty A, Rishi D, Abraham M. Management of oral submucous fibrosis with injection of hyaluronidase and dexamethasone in grade III oral submucous fibrosis: A retrospective study. J Int Oral Health. 2015;7(8):82-85.
Jaya Raja Kumar K, Muralidharan S, Arumugam Dhanaraj S. Development and in vitro evalution of guar gum based fluconazole in situ gel for oral thrush. J Pharm Sci Res. 2012;4(12):2009-2014.
Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release. 2000;67(2-3):357-368.
Jones DS, Woolfson AD, Brown AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int J Pharm. 1997;151(2):223-233.
Jones DS, Woolfson AD, Djokic J, Coulter WA. Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res. 1996a;13:1734-1738.
Kaplan M, Tuğcu-Demiröz F, Vural I, Çelebi N. Development and characterization of gels and liposomes containing ovalbumin for nasal delivery. J Drug Deliv Sci Tec. 2018;44:108-117.
Kapoor H, Aqil M, Imam SS, Sultana Y, Ali A. Formulation of amlodipine nano lipid carrier: Formulation design, physicochemical and transdermal absorption investigation. J Drug Deliv Sci Tech. 2019;49:209-218.
Karavana SY, Gökçe EH, Rençber S, Özbal S, Pekçetin Ç, Güneri P, et al. A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: In vivo/In vitro examinations. Int J Nanomed. 2012a;7:5693-5704.
Karavana SY, Rençber S, Ay Şenyiğit Z, Baloğlu E. A New in-situ gel formulation of itraconazole for vaginal administration. Pharmacol Pharm. 2012b;3:417-426.
Kima DH, Martin DC. Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. Biomaterials. 2006;27(15):3031-3037.
Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467-75.
Mahdi MH, Conway BR, Smith AM. Development of mucoadhesive sprayable gellan gum fluid gels. Int J Pharm. 2015;488(1-2):12-19.
Manson SC, Brown RE, Cerulli A, Vidaurre CF. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103(7):975-994.
Moolakkadath T, Aqil M, Ahad A, Imam SS, Praveen A, Sultana Y, Mujee M. Preparation and optimization offisetin loaded glycerol based softnanovesicles by Box-Behnken design. Int J Pharm. 2020;578:119125.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth. 1983;65(1-2):55-63.
Mythri G, Kavitha K, Rupesh Kumar M, Singh J. Novel mucoadhesive polymers-A review. J Appl Pharm Sci. 2011;01(08):37-42.
Nairy Matapady H, Charyulu NR, Gulzar Ahmed M, Prabhu P, Singh A, Subrahamanyam EVS. Development of a gellan gum based mucoadhesive in situ gels for buccal local delivery system of fluconazole. Int J Chem Sci. 2009;7(1):315-326.
O’Neil, M.J. (ed.). The Merck Index-An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th Edition, Whitehouse Station, NJ: Merck and Co., Inc., 2001, p. 518.
Özyazıcı M, Fırlak M, Tuncay Tanrıverdı S, Rençber S, Karavana SY, Vezir Kahraman M. Bioadhesive gel and hydrogel systems for buccal delivery of ketoprofen: preparation and in vitro evaluation studies. Am J Drug Delivery Ther. 2015;2(3):078-091.
Pandey P, Cabot PJ, Wallwork B, Panizza BJ, Parekh HS. Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels-a platform for therapeutic delivery to mucosal sinus tissue. Eur J Pharm Sci. 2017;96:499-507.
Peppas NA, Buri PA. Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Control Release. 1985;2:257-275.
Pereira Fernandes F, Campos Fortes A, Cruz Fonseca SG, Breitkreutz J, Gomes Ferraz H. Manufacture and characterization of mucoadhesive buccal films based on pectin and gellan gum containing triamcinolone acetonide. Int J Polym Sci. 2018;(2):1-10.
Petersen PE. Oral cancer prevention and control-the approach of the World Health Organization. Oral Oncol. 2009;45(4-5):454-460.
Ranch K, Patel H, Chavda L, Koli A, Maulvi F, Parikh RK. Development of in situ ophthalmic gel of dexamethasone sodium phosphate and chloramphenicol: A Viable alternative to conventional eye drops. J Appl Pharm Sci. 2017;7(03):101-108.
Rençber S, Aydın Köse F, Karavana SY. Dexamethasone-loaded PLGA-nanoparticles for potential local treatment of oral precancerous lesions. Pharm Dev Tech. 2020;25(2):149-158.
Rençber S, Karavana SY, Ay Şenyigit Z, Eraç B, Hoşgör Limoncu M, Baloğlu E. Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: Formulation, preparation and in vitro/in vivo evaluation. Pharm Dev Tech. 2017;22(4):551-561.
Rençber S, Karavana SY, Yengin Ç, Baloğlu E, Özer Ö. Key parameters of development of a generic semi-solid product. Lat Am J Pharm. 2019;38(3):523-30.
Rençber S, Karavana SY, Yılmaz FF, Eraç B, Nenni M, Özbal S, et al. Development, characterization and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis. Int J Nanomed. 2016;11:2641-2653.
Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5(1):37-42.
Sandri G, Rossi S, Ferrari F, Bonferonia MC, Muzzarelli C, Caramella C. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci. 2004;21(2-3):351-359.
Sankar V, Hearnden V, Hull K, Juras DV, Greenberg M, Kerr A, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis. 2011;17(Suppl 1):73-84.
Sarnes E, Crofford L, Watson M, Dennis G, Kan H, Bass D. Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther. 2011;33(10):1413-32.
Sato S, Miyake M, Hazama A, Omori K. Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue. Drug Chem Toxicol. 2014;37(3):268-275.
Scholz OA, Wolff A, Schumacher A, Giannola LI, Campisi G, Ciach T, et al. Drug delivery from the oral cavity: focus on a novel mechatronic delivery device. Drug Discov Today. 2008;13(5):247-253.
Sengel Türk CT, Sezgin Bayindir Z, Badilli U. Preparation of polymeric nanoparticles using different stabilizing agents. J Fac Pharm. 2009;38(4):257-268.
Senyiğit T, Sonvico F, Barbieri S, Ozer O, Santi P, Colombo P. Lecithin/chitosan nanoparticles of clobetasol-17-propionate capable of accumulation in pig skin. J Control Release. 2010;142(3):368-373.
Shaligram Mahajan H, Pramod Patil P. In situ cross linked chitosan-gellan gum polyelectrolyte complex based nanogels containing curcumin for delivery to cancer cells. Indian J Pharm Educ. 2017;51(2S):40-45.
Singh R, Lillard JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86(3):215-223.
Smith AM, Shelton RM, Perrie Y, Harris JJ. An initial evaluation of gellan gum as a material for tissue engineering applications. J Biomater Appl. 2007;22(3):241-254.
Sudhakar Y, Kuotsu K, Bandyopadhyay A. Buccal bioadhesive drug delivery-a promising option for orally less efficient drugs. J Control Release. 2006;114(1):15-40.
Sun C, Wang X, Zheng Z, Chen D, Wang X, Shi F, et al. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration. Int J Nanomed. 2015;10:3567-3579.
Survival Rates for Oral Cavity and Oropharyngeal Cancer”. www.cancer.org Retrieved 2019-03-10.
» www.cancer.org
Ujhelyi Z, Kalantari A, Vecsernyes M, Roka E, Fenyvesi F, Roka R, et al. The enhanced inhibitory effect of different antitumor agents in self-microemulsifying drug delivery systems on human cervical cancer hela cells. Molecules. 2015;20(7):13226-13239.
Varshosaz J, Tavakoli N, Saidian S. Development and physical characterization of a periodontal bioadhesive gel of metronidazole. Drug Deliv. 2002;9(2):127133.
Westedt U, Kalinowski M, Wittmar M, Merdan T, Unger F, Fuchs J, et al. Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment. J Control Release. 2007;119(1):41-51.
Yalkowsky SH, Yan H. Handbook of Aqueous Solubility Data: An extensive compilation of aqueous solubility data for organic compounds extracted from the aquasol database. CRC Press LLC, Boca Raton, FL. 2003, p. 1197.
Yang X, Trinh HM, Agrahari V, Sheng Y, Pal D, Mitra AK. Nanoparticle-based topical ophthalmic gel formulation for sustained release of hydrocortisone butyrate. AAPS Pharm Sci Tech. 2016;17(2):294-306.
Yardimci G, Kutlubay Z, Engin B, Tuzun Y. Precancerous lesions of oral mucosa. World J Clin Cases. 2014;2(12):866-872.
Downloads
Published
Issue
Section
License
Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content of the journal, except where identified, is licensed under a Creative Commons attribution-type BY.
The on line journal has open and free access.
How to Cite
Funding data
-
Ege Üniversitesi
Grant numbers 16/ECZ/015
