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

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 ≤v0.2); 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.

Nanoencapsulation of Rose-Hip Oil Prevents Oil Oxidation and Allows Obtainment of Gel and Film Topical Formulations

“…The zeta potential was found to be +9.8±1.5 due to the cationic properties of Eudragit RS 100®, used as nanocapsule shell. The positive zeta potential can increase the contact of the nanocapsules with the skin, due to negative charge of the tissue, as previously observed for the vaginal mucosae (29). The value obtained for the pH was 5.8±0.9, which is in agreement with previous similar nanocapsule aqueous suspensions (30).…”

Polymeric gels for intravaginal drug delivery

“…However, the particles used showed some irritancy in vivo. Solid Eudragit RS 100 and Eudragit S 100 nanoparticles measuring 200 nm were incorporated into a chitosan gel by Frank et al [93]. It was found that incorporating nanoparticles into a 2.5 % chitosan gel improved adhesion to porcine vaginal mucosa, as determined using a texture analyser.…”

Approaches in Polymeric Nanoparticles for Vaginal Drug Delivery: A Review of the State of the Art

“…The main advantage of this type of polymer is the positive charge that increases the capacity of mucoadhesion, residence time for prolonged release, and, above all, increased penetration capacity in the vaginal mucosa, unlike other nanocapsules, regardless of the gel in which it is incorporated. The formulation reached a depth of up to 3800 µm in the vaginal mucosa [ 70 ].…”

“…Chitosan is nontoxic, biocompatible, biodegradable, possesses good mechanical properties, good film-forming ability, and is bioadhesive; also, fungicidal and antimicrobial properties have been found. Frank et al [ 70 ] found that gels with a chitosan concentration of 2.5% w / w were those most suitable for vaginal delivery. Chitosan hydrogels exhibited higher adhesion to vaginal mucosa; in addition, the study indirectly revealed low interaction between the vehicle and the fluorescent-marked Eudragit ® RS nanoparticles because penetration of the lipophilic molecule model into the mucosa was high in comparison to when this was not nanoencapsulated.…”