Cyclodextrins (CyDs) were employed as protective stabilizers for the preparation of surfactant-free nanocrystals of indomethacin (IMC) by using the emulsion solvent diffusion method. The effect of changing the type and concentration of CyDs on the formation of IMC nanocrystals was investigated. Dispersions were freeze-dried to characterize the size, shape, nanoparticle yield, crystallinity, and dissolution behavior of the obtained particles. Submicron-sized particles of IMC with average diameters in the range of 300-500 nm were obtained by incorporating α-, β-, or γ-CyD in the outer phase of the primary emulsions. Quantitative determination demonstrated that more than 80% of IMC was recovered as fine particles smaller than 0.8 µm. The powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses of the freeze-dried samples confirmed the polymorphic change of IMC to the meta-stable form. A significant enhancement in the dissolution rate of IMC nanocrystals was observed when compared to the commercial powder.

The concept of mucoadhesion for the design of non-invasive drug delivery systems gained increasing attention in recent years. Within the current review, various mucoadhesive polymers, including poly(acrylates), chitosan, thiolated polymers and others, as well as their use in mucosal drug delivery are discussed. An emphasis has been put on the development of mucoadhesive formulations, and in particular on recently developed micro- and nanoparticulate systems. Moreover, the applications of the mucadhesive carrier systems for different administration routes such as the oral, nasal, pulmonary and ocular route are discussed.

Novel pH-sensitive nanospheres designed for colon-specific delivery were prepared using polymeric mixtures of poly (lactic-co-glycolic) acid (PLGA) and methacrylate copolymers. Budesonide (BSD), a topically active corticosteroid, was entrapped as a model drug. The therapeutic efficacy of the prepared nanospheres was assessed using the trinitrobenzenesulfonic acid (TNBS) colitis rat model, in comparison with conventional enteric microparticles. In addition, the colon targeting properties, systemic bioavailability, and specific uptake by the inflamed colon mucosa were evaluated using coumarin-6 (C-6) loaded nanospheres. The prepared nanospheres showed strongly pH-dependent drug release properties in acidic and neutral pH media followed by a sustained release phase at pH 7.4. Animal experiments revealed the superior therapeutic efficiency of BSD nanospheres in alleviating the conditions of TNBS-induced colitis model. The in-vivo studies using C-6-loaded nanospheres displayed higher colon levels and lower systemic availability of the fluorescent marker when compared with simple enteric coating. Moreover, quantitative analysis of the fluorescent marker and confocal laser scanning studies showed strong and specific adhesion of the nanospheres to the ulcerated and inflamed mucosal tissue of the rat colon. In conclusion, the proposed nanosphere system combined the properties of pH-sensitivity, controlled release, and particulate targeting that could be useful for colon-specific delivery in inflammatory bowel disease.