This work aimed to develop and evaluate pH-dependent systems based on nanospheres (NSphs) and nanocapsules (NCs) loaded with chlorhexidine (CHX) base as a novel formulation for the treatment of periodontal disease. Cellulose acetate phthalate (CAP) was employed as a pH-dependent polymeric material. The NSphs and NCs were prepared using the emulsion-diffusion technique and then characterized according to encapsulation efficiency (EE), size, zeta-potential, morphology, thermal properties, release profiles and a preliminary clinical panel test. The formulations showed 77% and 61% EE and 57% and 84% process efficiency (PE), respectively. Both systems were spherical with an average size of 250–300 nm. Differential scanning calorimetry (DSC) studies showed that the drug has the potential to be dispersed molecularly in the NSph matrix or dissolved in the oily center of the NCs. The CHX release test revealed that the release of NSphs-CHX follows Fickian diffusion involving diffusion-erosion processes. The NCs showed a slower release than the NSphs, following non-Fickian diffusion, which is indicative of anomalous transport. These nanosystems may, therefore, be employed as novel formulations for treating periodontal disease, due to (1) their coverage of a large surface area, (2) the controlled release of active substances at different pH, and (3) potential gingival tissue infiltration.

The aim of this work was to obtain pH-dependent nanofibers with an electrospinning technique as a novel controlled release system for the treatment of periodontal disease (PD). Cellulose acetate phthalate (CAP) was selected as a pH-sensitive and antimicrobial polymer. The NF was optimized according to polymeric dispersion variables, polymer, and drug concentration, and characterized considering morphology, diameter, entrapment efficiency (EE), process efficiency (PE), thermal properties, and release profiles. Two solvent mixtures were tested, and CHX-CAP-NF prepared with acetone/ethanol at 12% w/v of the polymer showed a diameter size of 934 nm, a uniform morphology with 42% of EE, and 55% of PE. Meanwhile, CHX-CAP-NF prepared with acetone/methanol at 11% w/v of polymer had a diameter of 257 nm, discontinuous nanofiber morphology with 32% of EE, and 40% of PE. EE and PE were dependent on the polymer concentration and the drug used in the formulation. Studies of differential scanning calorimetry (DSC) showed that the drug was dispersed in the NF matrix. The release profiles of CHX from CHX-CAP-NF followed Fickian diffusion dependent on time (t^0.43−0.45), suggesting a diffusion–erosion process and a matrix behavior. The NF developed could be employed as a novel drug delivery system in PD.