Spray-dried microparticles of encapsulated gefitinib for slow-release localized treatment of periodontal disease

Periodontal disease (PD) can be prevented by local or systemic application of epidermal growth factor receptor inhibitors (EGFRIs) that stabilize & alpha;v136 integrin levels in the periodontal tissue, leading to an increase in the expression of anti-inflammatory cytokines, such as transforming growth factor-131. Systemic EGFRIs have side effects and, therefore, local treatment of PD applied into the periodontal pockets would be preferrable. Thus, we have developed slow-release three-layered microparticles of gefitinib, a commercially available EGFRI. A combination of different polymers [cellulose acetate butyrate (CAB), Poly (D, L-lactide-co-glycolide) (PLGA) and ethyl cellulose (EC)] and sugars [D-mannose, D-mannitol and D-(+)-trehalose dihydrate] were used for the encapsulation. The optimal formulation was composed of CAB, EC, PLGA, mannose and gefitinib (0.59, 0.24, 0.09, 1, and 0.005 mg/ml, respectively; labeled CEP-gef), and created microparticles of 5.7 & PLUSMN; 2.3 & mu;m in diameter, encapsulation efficiency of 99.98%, and a release rate of more than 300 h. A suspension of this microparticle formulation blocked EGFR phosphorylation and restored & alpha;v136 integrin levels in oral epithelial cells, while the respective control microparticles showed no effect.