The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit^® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit^® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit^® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation.

Curcumin’s role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples’ collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages. This study investigated Vacuum Compression Molding (VCM) as a solvent-free manufacturing method for the preparation of flexible-dose pediatric orodispersible films. The experimental approach focused on selecting the appropriate plasticizer and ratios of the active pharmaceutical ingredient, diclofenac sodium, followed by the study of their impacts on the mechanical properties, disintegration time, and drug release profile of the ODFs. Additional investigations were performed to obtain insights regarding the solid-state properties. The ODFs obtained by VCM displayed adequate quality in terms of their critical characteristics. Therefore, this proof-of-concept study shows how VCM could be utilized as a standalone method for the production of small-scale ODFs, enabling the customization of doses to meet the individual needs of pediatric patients.

Using short interfering RNA (siRNA) to reduce the overexpression of pro-inflammatory cytokines associated with colitis proved effective, but co-administration with an antioxidant could significantly enhance therapeutic outcomes. The objective of this study was to develop a colon-targeted interleukin-6 (IL-6) siRNA and ascorbic acid (AA)-loaded polymeric nanoparticulate system (siRNA_AA NPs) and to investigate whether it can attenuate inflammation through synergistic anti-inflammatory and antioxidant effect in an experimental model of induced colitis. Trimethyl chitosan (TMC) nanoparticles (NPs) were prepared and characterized, and the influence of different formulation factors on their quality characteristics was evaluated, in order to select the most promising formulation to be tested in a model of colitis induced in mice. CD1 mice (n = 36) were divided into six groups. After induction of colitis, groups were treated by oral gavage with saline solution (healthy and disease control), prednisolone (reference), siRNA NPs (reference), scramble_AA NPs (reference), and siRNA_AA NPs (test). siRNA_AA NPs proved to be effective in the treatment of induced colitis, showing the most significant gene silencing of IL-6 and IL-1β as confirmed by PCR analysis. This silencing effect surpassed that observed with the reference treatment, prednisolone. Histopathological analysis indicated the ability of siRNA_AA NPs to induce repair processes of tissue damage, thus confirming the study hypothesis. The results obtained provide an important contribution regarding the effects obtained through combined targeting of the most important pathophysiological mechanisms involved in colitis, by simultaneous administration of antioxidants and nucleic acids inhibiting inflammatory cytokines.