Salivary stimulation by prolonged release films of pilocarpine in diabetic rats.

  • Jesús Israel Rodríguez Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • Rosa Isela Sánchez Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • Marianela Garza Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • María Argelia Nakagoshi Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • Juan Manuel Solis Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • Katiushka Arévalo Facultad de Odontología, Universidad Autónoma de Nuevo León.
  • Emmanuel Garza


Introduction: The local use of prolonged drug delivery in the oral cavity provides many advantages, increasing the pharmacologic action in the local desirable site, the reduction of the usual dose and reduced adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for the treatment of glandular hypofunction, however the diversity of the adverse effects limit their use.Objective: To evaluate the cytotoxicity of biofilms in adherent fibroblasts and their ability to release pilocarpine in vivo for prolonged time in the oral cavity of diabetic rats and the effect on salivary flow.Methods: Chitosan and HPMC (Methocel K4MCR) biofilms were prepared in 1% acetic acid, added with pilocarpine by magnetic stirring. The cytotoxicity of  biofilms was evaluated in adherent fibroblasts HS27 and assessed by neutral red technique. The sialogogue effect of biofilms was evaluated on the floor of the mouth in diabetic rats, then performing a histopathological analysis using hematoxylin and eosin staining and Masson trichrome. Results: Biofilms were biocompatible with 96% cell viability. It was posible to increase the stimulation of salivary flow in diabetic rats (6.36±0.987 mg/hr) compared to the control group (0.5±0.06 mg/hr). Histopathological analysis showed no inflammatory infiltrate present in the area of application of biofilms. Conclusion: Biofilms were biocompatible with high cell viability, also managed to considerably increase salivary flow in diabetic rats, without triggering an inflammatory infiltrate in the area of application, indicating that it is a product of sustained release biocompatible and safe for pilocarpine administration.

Author Biography

Jesús Israel Rodríguez, Facultad de Odontología, Universidad Autónoma de Nuevo León.
Editor de Journal of Oral Research.Asesor en Metodología de la Investigación.


1. Mortazavi H, Baharvand M, Movahhedian A, Mohammadi M, Khodadoustan A. Xerostomia due to systemic disease: A review of 20 conditions and mechanisms. Ann Med Health Sci Res. 2014;4(4):503-10.
2. Donat F, Jordá L, Mihi V. Tratamiento de la boca seca: puesta al día. Med Oral. 2004;9(4):273–9.
3. Bernardi R, Perin C, Becker F, Ramos G, Gheno G, Lopes L. Effect of pilocarpine mouthwash on salivary flow. Braz J Med Biol Res. 2002;35(1):105–10.
4. Napeñas J, Brennan M, Fox P. Diagnosis and treatment of xerostomia (dry mouth). Odontology. 2009;97(2):76–83.
5. Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: A literature review. Cancer. 2006;107(11):2525–34.
6. Romero A, Ibuki F, Nogueira F. Sialic acid reduction in the saliva of streptozotocin induced diabetic rats. Arch Oral Biol. 2012;57(9):1189–93.
7. Deepak D, Gopakumar R. Xerostomia, its Association with Oral Manifestation and Ocular Involvement: A Clinical and Biochemical Study. JIAOMR, 2011;23(4): 513-517.
8. Rayman S, Dincer E, Almas K. Xerostomia: Diagnosis and Management in Dental Practice. N Y State Dent J. 2010;76(2):24–7.
9. Babaee N, Zahedpasha S, Zamaninejad S, Gholizadehpasha A, Moghadamnia Y, Moghadamnia A. Effects of milk curd on saliva secretion in healthy volunteer compared to baseline, 2% pilocarpine and equivalent pH adjusted acetic acid solutions. Indian J Dent Res. 2011;22(4):547.
10. Sawaya A, Abreu I, Andreazza N, Eberlin M, Mazzafera P. Pilocarpine and related alkaloids in Pilocarpus Vahl (Rutaceae). Nova Sci Publ Inc. 2010;63–80.
11. Aframian D, Helcer M, Livni D, Robinson S, Markitziu A, Nadler C. Pilocarpine treatment in a mixed cohort of xerostomic patients. Oral Dis. 2007;13(1):88–92.
12. Nakamura N, Sasano N, Yamashita H, Igaki H, Shiraishi K, Terahara A, Asakage T, Nakao K, Ebihara Y, Ohtomo K, Nakagawa K. Oral pilocarpine (5mg t.i.d.) used for xerostomia causes adverse effects in Japanese. Auris Nasus Larynx. 2009;36(3):310–3.
13. Hua L, Kawasaki P, Pokala V, Hayes J. An Interprofessional Study of the Effects of Topical Pilocarpine on Oral and Visual Function. Health Interprofessional Pract. 2012;1(3):1-10.
14. Brimhall J, Jhaveri M, Yepes J. Efficacy of cevimeline vs. pilocarpine in the secretion of saliva: a pilot study: Efficacy of cevimeline vs. pilocarpine. Spec Care Dentist. 2013;33(3):123–127.
15. Noaiseh G, Baker J, Vivino F. Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren’s syndrome. Clin Exp Rheumatol. 2014;32(4):575–7.
16. Cavallari C, Fini A, Ospitali F. Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine. Eur J Pharm Biopharm. 2013;83(3):405–14.
17. Sánchez R, Damas R, Domínguez P, Cerezo P, Salcedo I, Aguzzi C. Uso de la HidroxiPropilMetilCelulosa (HPMC) en liberación modificada de fármacos. Farmaespaña Ind. 2010;48–51.
18. Tapia C, Soto D, Vergara L, Alburquerque C, Maccioni A, Matamata A, Hermosilla G, Bucarey S. Antifungal effect of high molecular weight chitosan on Candida spp isolated from clinical samples. Rev Chil Infectol. 2009;26(6):515–9.
19. Olivas I, García P, Martel A, Martinez R, Martínez A, Martínez C. Preparación y caracterización de compositos de quitosana/nanotubos de carbono. Rev Mex Ing Quím. 2009;8(2):205–11.
20. De Carvalho M, Stamford T, Pereira E, Dos Santos P, Sampaio F. Chitosan as an oral antimicrobial agent. Formatex 2011. 2012;1(13): 542-550.
21. Juliano C, Cossu M, Pigozzi P, Rassu G, Giunchedi P. Preparation, In Vitro Characterization and Preliminary In Vivo Evaluation of Buccal Polymeric Films Containing Chlorhexidine. AAPS Pharm Sci Tech. 2008;9(4):1153–8.
22. Siddaramaiah, Kumar P, Divya K, Mhemavathi B, Manjula D. Chitosan/HPMC Polymer Blends for Developing Transdermal Drug Delivery Systems. J Macromol Sci Part A. 2006;43(3):601–7.
23. Miyazaki S, Kawasaki N, Nakamura T, Iwatsu M, Hayashi T, Hou WM, Attwood D. Oral mucosal bioadhesive tablets of pectin and HPMC: in vitro and in vivo evaluation. Int J Pharm. 2000;204(1):127–32.
How to Cite
RODRÍGUEZ, Jesús Israel et al. Salivary stimulation by prolonged release films of pilocarpine in diabetic rats.. Journal of Oral Research, [S.l.], v. 4, n. 2, p. 103-108, jan. 2015. ISSN 0719-2479. Available at: <>. Date accessed: 13 aug. 2020. doi:


Hyposalivation, Cytotoxicity, Rats, Pilocarpine, Biofilms.

Most read articles by the same author(s)