Design and biological response of doxycycline loaded chitosan microparticles for periodontal disease treatment

•EC coated CS/TPP MPs showed controlled release of doxycycline hyclate.•Mixed polymer surface of EC coated CS/TPP MPs exhibited high muco/bioadhesion.•MPs didn’t affect the viability of the tested epithelial cell line.•MPs induced slow and graduate apoptosis during 24 h in RAW264.7 cell line.•CS/TPP & EC coated CS/TPP MPs potentiate the anti-inflammatory effect of doxycycline. The aim of this study was to develop chitosan (CS) microparticulated mucoadhesive drug delivery system (DDS) with improved therapeutic performance and biological responce. Ionotropic gelation/spray drying process was used for preparation of doxycycline hyclate (DOXY) loaded low and medium molecular weight (LMw and MMw) CS/sodium tripolyphosphate microparticles (CS/TPP MPs), further coated with ethyl cellulose (EC) using coacervation/solvent displacement technique. The relevant physico-chemical and biopharmaceutical properties were optimized using experimental design approach. Both coated and uncoated CS/TPP MPs showed high mucoadhesive potential and did not affect the viability of the tested epithelial cell line. The MPs induced slow and gradual apoptotic response in murine macrophage cell line RAW 264.7 and the observed effect depended upon formulation type and MP concentration. Biological effect of the CS-based MPs observed in our experiments point to synergism of the biological response of the carrier with the anti-inflammatory effect of DOXY.