Chitosan gel containing polymeric nanocapsules: a new formulation for vaginal drug delivery

Luiza A Frank,¹ Giuseppina Sandri,² Francesca D´Autilia,² Renata V Contri,¹ Maria Cristina Bonferoni,² Carla Caramella,² Alejandro G Frank,³ Adriana R Pohlmann,¹ Silvia S Guterres<sup>1

1</sup>Pharmaceutical Science Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; ²Department of Drug Sciences, University of Pavia, Pavia, PV, Italy; ³Department of Industrial Engineering, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

Abstract: The vaginal route of administration is an alternative for several treatments for either local or systemic pharmacological effects. However, the permanence of a drug in this route represents a challenge for formulation development that can be overcome by using nanoencapsulation and chitosan gel. Thus, this work aimed to evaluate the performance of chitosan hydrogels containing cationic and anionic acrylic-based nanocapsules (Eudragit^® RS 100 and Eudragit^® S 100, respectively) with Nile red as a model of lipophilic substance in the vaginal route of administration, as measured by increases in the residence time and the penetration of these formulations. Several formulations were prepared with increasing chitosan concentrations, and were analyzed in terms of pH and rheological behavior so that the most suitable formulation could be selected. The enhancement of the adhesion (tensile stress test and washability profile) and penetration (confocal laser scanning microscopy and extraction followed by quantification) properties of the formulations, when applied to porcine vaginal mucosa, were evaluated. The nanocapsule suspensions produced presented adequate properties: size of approximately 200 nm (polydispersity index of ≤0.2); zeta potential around +10 mV for the cationic formulation and -10 mV for the anionic formulation; and pH values of 6.1±0.1 (Eudragit RS 100), 5.3±0.2 (Eudragit S 100), 6.2±0.1 (Nile red loaded Eudragit RS 100), and 5.1±0.1 (Nile red loaded Eudragit S 100). The chitosan formulation presented suitable viscosity for vaginal application and acidic pH (approximately 4.5). The tensile stress test showed that both formulations containing polymeric nanocapsules presented higher mucoadhesion when compared with the formulation without nanocapsules. In the washability experiment, no significant differences were found between formulations. Confocal microscopy and fluorescence quantification after extraction from the mucosa showed higher penetration of Nile red when it was nanoencapsulated, particularly in cationic nanocapsules. The formulations developed based on chitosan gel vehicle at 2.5% weight/weight containing polymeric nanocapsules, especially the cationic nanocapsules, demonstrated ­applicability for the vaginal delivery of hydrophobic substances.

Keywords: Eudragit^® RS 100, Eudragit^® S 100, vaginal route, nanotechnology

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