Design and Characterization of Mucoadhesive Gelatin-Ethylcellulose Microparticles for the Delivery of Curcumin to the Bladder

Abstract

Background: Bladder cancer is the second type of malignant carcinoma of the urinary tract. The treatment is time-consuming and requires maintenance doses of the drug for long period of time with important side effects. Curcumin has shown evident clinical advances in the treatment of cancer. The technology of microencapsulation and the use of mucoadhesive materials can contribute to modify the delivery and improve the bioavailability of curcumin.

Objective: The aim of this study was to design and characterize mucoadhesive microparticles containing curcumin using multivariate analysis and the spray-drying technique.

Methods: A factorial design 32+1 was employed to investigate the influence of gelatin, ethylcellulose, and curcumin on size, polydispersity index, drug content and entrapment efficiency. Microparticles were also evaluated by ATR-FTIR, X-ray diffraction, antioxidant activity, in-vitro release profile, exvivo mucoadhesion performance, and in-vitro cytotoxicity.

Results: Microparticles showed non-uniform surface, mean diameter from 2.73 µm to 4.62 µm and polydispersity index from 0.72 to 1.09, according to the different combinations of the independent factors. These independent variables also had a significant effect on the drug content. The highest values of drug trapping efficiency were obtained with the highest concentration of curcumin and polymers. Formulations displayed slow drug release and important antioxidant activity. The good mucoadhesive performance of microparticles was assessed by the falling film technique. Moreover, the formulations did not display in vitro toxicity against Artemia salina and Fibroblasts LM(TK).

Conclusion: The design results were useful for developing of curcumin dosage form with good physicochemical characteristics and mucoadhesive properties for the bladder administration.

Keywords: Factorial design; curcumin; drug release; microparticles; mucoadhesive; physicochemical properties..