Budesonide (BUD) is used as first choice therapy for the treatment of allergic rhinitis, a chronic allergic-immune condition with an increased incidence in the pediatric population. The main problem of BUD nasal formulations is related to its poor aqueous solubility (S0 = 5.03·10-5 M), sometimes compensated by the administration of high doses of the drug. The ability of thiolated hydroxypropyl-β-cyclodextrin (HP- β -CD-SH, 100 mM) to increase the water solubility of BUD (SHP- β-CD-SH = 10.9·10-3 M) more than pristine hydroxypropyl- β -cyclodextrin (HP- β-CD, SHP- β-CD = 4.3·10-3 M) has been previously demonstrated. Considering that S-protected thiomers have the advantage of increasing the stability of thiols over a wide pH range prolonging their residence time at the target site, 2-mercapto-nicotinic acid (MNA) was used in this study to protect the free thiol groups on HP- β -CD-SH generating the corresponding S-protected cyclodextrin (HP-β-CD-MNA). Besides, given the increased stability and processability of HP-β-CD-MNA, mucoadhesive microparticles (MPs) were prepared via spray-drying of aqueous solutions of the inclusion complex HP-β-CD-MNA/BUD. MPs were morphologically and dimensionally homogeneous exhibiting an average diameter of 3.24 ± 0.57 µm. Over time these MPs formed larger aggregates with an average diameter of 10–50 μm, suitable for the design of intranasal delivery systems. Differential scanning calorimetry analyses revealed the absence of crystalline BUD from spray-dried complexes. Dissolution studies shown that spray-dried MPs dissolved quickly and the complexed drug was completely solubilized within the first 20 min of the dissolution process. Cell viability assay indicated that spray-dried complexes are safe. In vitro mucoadhesion studies on freshly excised porcine nasal mucosa showed a 1.4- and 2.3-fold prolonged mucosal residence time of HP- β -CD-SH/BUD and HP-β-CD-MNA/BUD in comparison to the unmodified cyclodextrin (CD), respectively. Rheological behaviour of spray-dried MPs complexes/mucus mixtures confirmed the results of the mucoadhesion studies, as the dynamic viscosity of the spray-dried inclusion complexes HP-β-CD-SH/BUD and HP-β-CD-MNA/BUD was 1.1-fold and 2.4 fold increased in comparison to the unmodified HP-β-CD/BUD complex. According to these results, MPs comprising HP- β -CD-MNA/BUD might be a promising tool for nasal delivery of poorly water-soluble corticosteroids such as BUD.