Toward the development of microparticulate carriers for nasal administration, N-trimethylchitosan chloride (TMC) of low molecular weight (LMW) and high molecular weight (HMW) and low degree of quaternization (16% and 27%, respectively) was co-formulated into microparticles comprising of dipalmatoylphosphatidylcholine (DPPC) and poly(lactic-co-glycolic) acid (PLGA) via the spray-drying technique. The chitosan derivatives were characterized by means of nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and Fourier transfrom infrared (FTIR) spectroscopy. The size and morphology of the produced microparticles were assessed by scanning electron microscopy (SEM), whereas their mucoadhesive properties were investigated by means of atomic force microscopy-force spectroscopy (AFM-FS). The results showed that microparticles exhibit mucoadhesion when TMC is present on their surface above a threshold of TMC (>0.3% w/w).