Fabrication and optimization of itraconazole-loaded zein-based nanoparticles in coated capsules as a promising colon-targeting approach pursuing opportunistic fungal infections.

Itraconazole (ITZ), a broad-spectrum antifungal drug, was formulated into colon-targeting system aiming to treat opportunistic colonic fungal infections that commonly infect chronic inflammatory bowel diseases (IBD) patients due to immunosuppressive therapy. Antisolvent precipitation technique was employed to formulate ITZ-loaded zein nanoparticles (ITZ-ZNPs) using various zein: drug and aqueous:organic phase ratios. Central composite face-centered design (CCFD) was used for statistical analysis and optimization. The optimized formulation was composed of 5.5:1 zein:drug ratio and 9.5:1 aqueous:organic phase ratio with its observed particle size, polydispersity index, zeta potential, and entrapment efficiency of 208 ± 4.29 nm, 0.35 ± 0.04, 35.7 ± 1.65 mV, and 66.78 ± 3.89%, respectively. ITZ-ZNPs were imaged by TEM that revealed spherical core-shell structure, and DSC proved ITZ transformation from crystalline to amorphous form. FT-IR showed coupling of zein NH group with ITZ carbonyl group without affecting ITZ antifungal activity as confirmed by antifungal activity test that showed enhanced activity of ITZ-ZNPs over the pure drug. Histopathological examination and cytotoxicity tests ensured biosafety and tolerance of ITZ-ZNPs to the colon tissue. The optimized formulation was then loaded into Eudragit S100-coated capsules and both in vitro release and in vivo X-ray imaging confirmed the success of such coated capsules in protecting ITZ from the release in stomach and intestine while targeting ITZ to the colon. The study proved that ITZ-ZNPs is promising and safe nanoparticulate system that can protect ITZ throughout the GIT and targeting its release to the colon with effectual focused local action for the treatment of colon fungal infections.

Exploiting itraconazole-loaded nanomixed micelles in coated capsules as efficient colon-targeted delivery system for improved antifungal and potential anticancer efficacy.

Chronic Inflammatory bowel diseases are usually accompanied by opportunistic colonic fungal infections. Itraconazole (ITZ), is a highly lipophilic broad-spectrum antifungal drug that is superiorly effective against several fungal species. Box-Behnken design was adopted to design ITZ-nanomixed micelles (ITZ-NMMs), aiming to enhance ITZ solubility, using various concentrations of Pluronic® L121, Cremophor EL, and with either sodium-deoxycholate or Pluronic® F68 through thin film hydration technique. Optimized formula composed of 90 % Pl-L121, 9.1% Cremophor EL, 3.127 % ITZ concentration and SDC as the hydrophilic surfactant and its particle size, Polydispersity index, zeta potential, entrapment efficiency, and release extent after 3 h were found to be 17.82 ± 0.189 nm, 0.26 ± 0.014, -6.72 ± 0.725 mV, 66 ± 7.4%, and 96.3 ± 7.22%, respectively. In vitro ITZ release study implied the ability of optimal ITZ-NMMs to enhance ITZ solubility in comparison to ITZ suspension. Also, augmented anti-fungal and anti-cancer activities were proven as ITZ-NMMs IC50 was 16.5 times that of pure ITZ. Afterwards, lyophilized optimal ITZ-NMMs formula was loaded into Eudragit S100-coated capsules where in vitro release and in vivo X-ray imaging ensured protection of ITZ release in either the stomach or intestine and targeting it to the colon. Such results suggested promising ITZ-NMMs system, capable of enhancing ITZ solubility in the intended target site, therefore, can be used not only in the treatment of colon fungal infections but also augments colon cancer therapy.