Formulation and optimization of theophylline-loaded enteric-coated spanlastic nanovesicles for colon delivery; Ameliorate acetic acid-induced ulcerative colitis

Treatment of colon diseases presents one of the most significant obstacles to drug delivery due to the inability to deliver sufficient drug concentration selectively to the colon. The goal of the proposed study was to develop, optimize, and assess an effective colon target delivery system of theophylline-based nanovesicles (TP-NVs) surrounded by a biodegradable polymeric shell of chitosan (CS) and Eudragit L100 (E_L100) for the treatment of ulcerative colitis (UC). TP-loaded nanovesicles were fabricated using the ethanol injection method and coated with CS and E_L100, respectively. We used a 3²-factorial design approach to optimize the concentration of CS and E_L100 to minimize particle size (PS) and maximize the cumulative amount of theophylline released (CTR) after 24 h. The optimized formulation was described using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and in vitro release. In-vivo quantification of theophylline in the gastrointestinal tract and in-vivo targeting potential in a rat model of acetic acid-induced colitis were also thoroughly evaluated. The characteristics of the optimal formula predicted by the 3²-factorial design approach corresponded exceptionally well with the measured PS of 271.3 nm, the zeta potential of -39.9 mV, and CTR of 3.95, and a 99.93% after 5 and 24 h, respectively. Notably, the in vivo results in the rat model of colitis showed that the formulation with an optimized coat significantly improved theophylline distribution to the colon and markedly decreased the expression of interleukin-6 and ulcerative lesions compared to a pure theophylline solution. These outcomes elucidated the feasibility of a 3²-factorial design to detect the crucial interactions between the study's components. Our findings suggested that enteric-coated nanovesicles formulations with optimal coat compositions of 0.2693% (w/v) and 0.75% (w/v) of CS and E_L100, respectively, were promising carriers for colonic delivery of theophylline, a rate-limiting step in the treatment of UC.