Physico-chemical and antimicrobial evaluation of chitosan and hydroxypropyl methylcellulose biofilms for prolonged release of pilocarpine.

Jesús Israel Rodríguez, Rosa Isela Sánchez, Marianela Garza, María Argelia Nakagoshi, Juan Manuel Solis, Katiushka Arévalo, Emmanuel Garza

Abstract


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: The principal aim of this study is analyze the physical and chemical properties of biofilms including the pH, thickness, solubility, consistency and the ability to release for prolonged time pilocarpine, and also assess the antimicrobial activity in two opportunistic pathogens in hyposialia (Streptococcus mutans and Candida albicans). Methods: Chitosan and HPMC (Methocel K4MCR) biofilms were prepared in 1% acetic acid, added with pilocarpine by magnetic stirring, assessing the pH, thickness and time of solubility in artificial saliva, as well as the uniformity of distribution and kinetics drug release per cm2 by spectrophotometry (OD = 420nm). The antimicrobial activity was test by disk diffusion against St. mutans ATCC 700610 and C. albicans ATCC 90029 at concentrations of hyposalivation (1.44 x 1.2 x 106 CFU and 103 CFU, respectively).Results: All biofilms, except for Hydroxypropylmethylcellulose and Hydroxypropylmethylcellulose / Pilocarpine formulation were found to have the optimal physicochemical properties for handling, maintaining a uniform distribution of the drug in 76% per cm2 with extended release during 4 hours, but showing negative antimicrobial activity in concentrations of hyposalivation.Conclusion: The films had optimum handling properties, and constant release of the drug, however, antimicrobial activity was not found.

Keywords


Biofilms, Pilocarpine, Hyposalivation, Chitosan.

References


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.

Nagpal K, Singh S, Mishra D. Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull. 2010;58(11):1423–30.

Park Y, Lee Y, Park S, Sheen S, Chung C, Lee S. Platelet derived growth factor releasing chitosan sponge for periodontal bone regeneration. Biomaterials. 2000;21:153–9.

Verma A, Kumar A, Kumar S. Preparation of hydrophilic swelling controlled-release floating matrix tablets containing hpmc and chitosan. Int J Pharm Pharm Sci. 2012;4:82–7.

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

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.

De Moura M, Avena R, McHugh T, Krochta J, Mattoso L. Properties of Novel Hydroxypropyl Methylcellulose Films Containing Chitosan Nanoparticles. J Food Sci. 2008 8;73(7):31–37.

Cedillo E, Hernández A, Villafuerte L. Efecto del bicarbonato de sodio sobre la flotación y la liberación controlada de metronidazol desde matrices de Methocel K4M y Carbopol 971P NF. Rev Mex Cienc Farm. 2007;38(2):33–41.

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.

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.

Rotta J, Ozório R, Kehrwald A, de Oliveira Barra G, de Melo R, Barreto P. Parameters of color, transparency, water solubility, wettability and surface free energy of chitosan/hydroxypropylmethylcellulose (HPMC) films plasticized with sorbitol. Mater Sci Eng C. 2009;29(2):619–23.

Archana D, Dutta J, Dutta PK. Evaluation of chitosan nano dressing for wound healing: Characterization, in vitro and in vivo studies. Int J Biol Macromol. 2013;57:193–203.

Lavertu M, Darras V, Buschmann MD. Kinetics and efficiency of chitosan reacetylation. Carbohydr Polym. 2012;87(2):1192–8.

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.

Kim T, Ahn J, Choi H, Choi Y, Cho C. A novel mucoadhesive polymer film composed of carbopol, poloxamer and hydroxypropylmethylcellulose. Arch Pharm Res. 2007;30(3):381–6.

Ofori K, Fell J. Biphasic drug release: the permeability of films containing pectin, chitosan and HPMC. Int J Pharm. 2001;226(1):139–45.

Ofori K, Fell J. Leaching of pectin from mixed films containing pectin, chitosan and HPMC intended for biphasic drug delivery. Int J Pharm. 2003;250(1):251–7.

Perioli L, Ambrogi V, Angelici F, Ricci M, Giovagnoli S, Capuccella M. Development of mucoadhesive patches for buccal administration of ibuprofen. J Controlled Release. 2004;99(1):73–82.

Yehia S, El-Gazayerly O, Basalious E. Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release. AAPS PharmSciTech. 2008;9(4):1207–17.

Wong C, Yuen K, Peh K. An in-vitro method for buccal adhesion studies: importance of instrument variables. Int J Pharm. 1999;180(1):47–57.

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.

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.

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.

Bernardi R, Perin C, Becker FL, Ramos GZ, Gheno GZ, Lopes LR. Effect of pilocarpine mouthwash on salivary flow. Braz J Med Biol Res. 2002;35(1):105–10.

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.

Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: A literature review. Cancer. 2006 1;107(11):2525–34.

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.

Gallardo J. Xerostomía: etiology, diagnosis and treatment. Rev Med Inst Mex Seguro Soc. 2008;46(1):109–16.

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 PharmSciTech. 2008;9(4):1153–8.

Zhou H, Hao J, Wang S, Zheng Y, Zhang W. Nanoparticles in the ocular drug delivery. Int J Ophthalmol. 2013;18;6(3):390–6.


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