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

Introduction: The local use of prolonged drug delivery in the oral cavity provides many advantages, i.e., it increases pharmacologic actions in the desired local site, allows smaller doses and reduces adverse effects. Pilocarpine is a cholinergic drug approved by the FDA for treating glandular hypofunction; however, the adverse effects associated with it limit its use. Objective: To evaluate cytotoxicity of films in adherent fibroblasts and their ability to release pilocarpine in vivo for a prolonged time in the oral cavity of diabetic rats and its effect on salivary flow.Methods: Chitosan and Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1% acetic acid and pilocarpine was added under magnetic stirring. Cytotoxicity of films was evaluated in adherent fibroblasts HS27 and assessed by neutral red technique. The sialogogue effect of films was evaluated on the floor of the mouth of diabetic rats. Later, histopathological analysis was performed using hematoxylin and eosin and Masson’s trichrome stains. Results: Films were biocompatible and had 96% cell viability. It was possible to increase stimulation of salivary flow in diabetic rats (6.36±0.987mg/hr) compared to the control group (0.5±0.06mg/hr). The histopathological analysis did not show inflammatory infiltrate in the area where films were placed. Conclusion: Films were biocompatible and had high cell viability. Also, they considerably increased salivary flow in diabetic rats, without triggering an inflammatory infiltrate in the area which indicates that it is a biocompatible product for sustained release and safe for pilocarpine administration.