Desenvolvimento e avaliação de implantes mucoconjuntivais biodegradáveis constituídos de quitosana para o tratamento de oftalmopatias

Abstract

Colliryum and ointment represent the majority of topical preparations for ophthalmic diseases. Mucoconjunctival films represent alternative methods aimed at improving conventional ocular therapy. Chitosan is a polysaccharide obtained through the deacetylation of chitin. Biodegradability, biocompatibility, and non-toxicity are included in favorable biological properties, which allow for their use as vehicles for ophthalmic formulations. Mucoconjunctival films with timolol maleate and ofloxacin were produced and evaluated in vivo for the treatment and prevention of glaucoma and external ocular infection. Chitosan drug-loaded films were produced by a casting/solvent evaporation technique. The presence of the drugs on biopolymers was confirmed by means of swelling studies, attenuated total reflectance fourier transformed infrared spectroscopy spectral data, differential scanning calorimetry analyses, and in vitro studies. No significant difference could be observed between ofloxacin-loaded chitosan films and sterile disks soaked in 0.3% ofloxacin within a bacterial kill zone of Staphyloccocus aureus and Pseudomonas aeruginosa (P<0.05). In thisin vitro study, 80% of the drug was released from the films at1 h and 14 days after application for timolol maleate and ofloxacin, respectively. Maximum release in vivo was 5 days after application for timolol maleate and 10 weeks for ofloxacin. No significant difference in the lowering of intraocular pressure in rabbits treated with 0.5% timolol maleate, as compared to those that received the films (P<0.05), could be observed. Ofloxacin concentration on tears of animals that received 0.3% ofloxacin was 121.09 ± 10.84 (Cmax µg/mL) and leveled off at 7 h at 12.61 ± 1.78 (Cmin µg/mL) with AUC(0.5-7h) = 191.36 ± 16.60 µg/mL. In rabbits that received ofloxacin-loaded chitosan films, the tear concentration of the drug peaked at 0.5 h to a level of1095.54 ± 121.59 (Cmax µg/mL) and leveled off at 120 h at 12.78 ± 1.39 (Cmin µg/mL) with AUC(0.5-120h) = 13524.09 ± 2263.81µg/mL. No statistically significant difference could be observed in ofloxacin concentrations in animals treated with 0.3% ofloxacin at 2 h after administration (35.13 ± 5.26) and 72 h following drug-loaded chitosan administration (33.60 ± 3.23) (P=0.4544). Similarly, no statistically difference could be observed at 7 h in animals treated with 0.3% ofloxacin (12.61 ± 1.78) and 120 h or 5 days using chitosan films (12.78 ± 1.39) (P=0.8336). No important signs of ocular discomfort or irritations could be identified. Ophthalmic structures that came in direct contact with the films revealed no alterations within histopathologic studies. Moreover, the animals showed no signs of ocular discomfort during the experimental assays. These findings suggest that the drug-loaded chitosan film is safe and efficient and presents a promising future as an ocular drug delivery system in the treatment and prevention of glaucoma and external ocular infection.