Cell lines

C.albicans SC5314

Preparation Method

Standardized C. albicans SC5314 (1×10⁶cells/ml) were inoculated in RPMI with or without Pilocarpine HCl on Thermanox coverslips (13mm) within a 24-well tissue culture plate and then incubated for 24h at 37℃.

Reaction Conditions

0-50mM

Applications

Light microscopy revealed that Pilocarpine HCl inhibited filamentation and biofilm formation in a dose-dependent manner. Furthermore, visually, in the presence of increasing concentrations of Pilocarpine HCl, more C.albicans cells maintained a yeast morphology, suggesting that Pilocarpine HCl was inhibiting the yeast-to-hypha transition. Scanning electron microscopy analysis further confirmed the fact that Pilocarpine HCl inhibited biofilm formation due to inhibition of the yeast-to-hypha transition in a dose-dependent manner.

Animal models

Male Sprague-Dawley rats, seven-week-old

Preparation Method

Each rat was fasted overnight before the experiment, but had free access to drinking water. The rat was anaesthetized with urethane (1.25 g/kg, s.c.) and its body temperature was maintained at 37℃ during the subsequent experiment. After intubating the trachea, the duct of the right parotid gland was cannulated for the collection of saliva. Pilocarpine hydrochloride (0.05, 0.1, 0.2 or 0.4mg/kg in 1mL) or distilled water was administered intraduodenally and the saliva was collected for 120min after this administration

Dosage form

0.05, 0.1, 0.2 or 0.4mg/kg in 1mL

Applications

The mean salivary output for 120min without pilocarpine hydrochloride was 1.58±0.99μL (n=6). Pilocarpine hydrochloride (0.05-0.4mg/kg, intraduodenal) dose-dependently increased salivary output for 120 min in normal rats, the total volumes being 3.02±0.73μL (0.05mg/kg; n=6), 3.91±0.50μL (0.1mg/kg; n=6; P

Pilocarpine HCl is a miotic drug that acts as a M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist, causing ciliary muscle contraction that opens up the trabecular meshwork which allows aqueous humour drainage and a resultant reduction in IOP^[1]. Pilocarpine HCl is a hydrophilic drug used for managing IOP in the treatment of glaucoma^[2]

Pilocarpine HCl encapsulated by liposomes can keep their integrity and physicochemical properties for at least 15 month^[3].Pilocarpine HCl specifically inhibits Candida albicans biofilm formation and pathogenicity through interaction with a muscarinic-like receptor^[4]. Pilocarpine HCl has acaricidal activity on larvae (LC₅₀=2.6 mgomL^-1) and engorged females (LC₅₀=11.8 mgomL^-1) of R.(B.) microplus^[5]

Pilocarpine HCl have apparent functional protective effects in xerostomia models: an increase in the volume of saliva without any change in salivary content. This prophylactic action of pilocarpine HCl may provide a new clinical treatment for irradiation xerostomia in patients with head and neck cancer^[6]. Oral activity responses to pilocarpine HCl are enhanced in neonatal 6-OHDA-treated rats^[7]

References:
[1]. Jain N, Verma A, et al. Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits. Drug Deliv. 2020;27(1):888-899.
[2]. Owodeha-Ashaka K, Ilomuanya MO, et al. Evaluation of sonication on stability-indicating properties of optimized pilocarpine hydrochloride-loaded niosomes in ocular drug delivery [published correction appears in Prog Biomater. 2021 Oct 5;:]. Prog Biomater. 2021;10(3):207-220.
[3]. Monem AS, Ali FM, et al. Prolonged effect of liposomes encapsulating pilocarpine HCl in normal and glaucomatous rabbits. Int J Pharm. 2000;198(1):29-38.
[4]. Nile C, Falleni M, et al. Repurposing Pilocarpine Hydrochloride for Treatment of Candida albicans Infections. mSphere. 2019;4(1):e00689-18. Published 2019 Jan 23.
[5]. Castro KN, Lima DF, et al. In vitro effects of Pilocarpus microphyllus extracts and pilocarpine hydrochloride on Rhipicephalus (Boophilus) microplus. Rev Bras Parasitol Vet. 2016;25(2):248-253.
[6]. Asari T, Komatsu Y, et al. Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats. Clin Exp Pharmacol Physiol. 2001;28(7):545-550.
[7]. Kostrzewa RM, Neely D. Enhanced pilocarpine-induced oral activity responses in neonatal 6-OHDA treated rats. Pharmacol Biochem Behav. 1993;45(3):737-740.