## 1 Introduction  
The preparation of microparticles based on hydrophilic polymers, such as polysaccharides derivatives, using techniques based on emulsion templates, majorly requires the use of organic solvents in order to form the hydrophilic and hydrophobic phases in which the internal hydrophilic phase contains the polymer [1; 2; 3]. In addition, together with the use of crosslinkers such as glutaraldehyde and terephthalaloyl chloride, the microparticles produced by this way may present an important degree of toxicity [1; 4].  
Xylan, which is the second most abundant polysaccharide of the biosphere, is mainly presented in hardwood and perennial plants such as grasses, cereals, and herbs [5]. The use of xylan for biomedical applications is based on its important biocompatibility and selective degradation in the gastrointestinal tract, which occurs in the colon through enzymatic hydrolysis by the microbiota. Our group has lately exploited this feature in order to develop colon-specific drug delivery systems [6; 7; 8].  
As previously mentioned, the preparation of polysaccharide-based microparticles, including xylan-based microparticles (XBM), mostly requires the use of organic/harmful solvents such as cyclohexane, and crosslinkers, such as terephthalaloyl chloride, during their preparation [1; 9; 10]. On this behalf, the water-in-water emulsion approach can produce microparticles by the mixture of two immiscible aqueous polymeric solutions. Once these solutions are mixed, there is a formation of a system with a positive Gibbs free energy (\(\Delta G\)) (Equation (1)).  
\[\Delta G=\Delta H_{\mathrm{mix}}-\mathrm{T}\;\Delta S_{\mathrm{mix}} \tag{1}\]  
This phenomenon happens due to the high molecular weight of the polyethylene glycol (PEG), which limited the translational motion of the polymeric chains. This results in a smaller value of \(\Delta S_{\mathrm{mix}}\) than \(\Delta H_{\mathrm{mix}}\). Hence, it results in a positive \(\Delta G\), and, therefore, leads to phase separation [11]. Similarly to the traditional oil-in-water and water-in-oil emulsions, these two polymeric phases, once homogenized, may form two different phases, which include a continuous and a discontinuous one. Thus, once the two phases are obtained and a crosslinker is added to the dispersion, particles can be obtained [12; 13].  
The reports about microparticles prepared by the water-in-water emulsion technique hardly ever describe the encapsulation of active molecules [14; 15; 16]. Nonetheless, when tried, the encapsulated molecules are mostly biomolecules, such as proteins and peptides [17]. A probable explanation for such a phenomenon would be related to the free mobility of the small hydrophilic molecules into the dispersion. Once both phases are aqueous, the encapsulation efficiency is hindered [14].  
The preparation of microparticles loaded with small active molecules through the water-in-water emulsion technique has been a pharmaceutical technology-based challenge. In this sense, in the present work, xylan microparticles loaded with mesalamine (5-ASA), which is a low molecular weight molecule, were prepared through a water-in-water emulsification process using different crosslinking approaches, designed through a \(2^{3}\) full factorial design with a central point.