Influence of formulation parameters on encapsulation of doxycycline in PLGA microspheres prepared by double emulsion technique for the treatment of periodontitis

Advanced therapeutics often employ controlled release of pharmaceutics by the use of microspheres. However, common techniques to produce microspheres suffer from poor encapsulation efficiency (EE) of hydrophilic drugs. The aim of this study was to assess various formulation parameters to enhance doxycycline (DOX) encapsulation into poly(D, L-lactide-co-glycolide) (PLGA) microspheres prepared by double emulsion (water/oil/ water) solvent evaporation technique. The parameters included variations in co-solvents, external aqueous phase (W-2) pH, and PLGA end-groups (ester- or acid-terminated). Results showed that the formulated microspheres sized < 10 mu m and were of low polydispersity. Furthermore, an external phase pH of 9.0 was most suitable for the incorporation of the drug. Additionally, the replacement of the polymer phase with a co-solvent system (1:5, EtOH:DCM %) significantly enhanced the drug EE using acid-terminated PLGA polymer. Drug release kinetics showed an initial burst release phase, followed by a controlled exponential phase that lasted up to 21 days. Furthermore, in vitro studies revealed concentration-dependent toxicity using periodontal ligament cells (PDLCs) and antibacterial properties against periodontal pathogens. Overall, this study demonstrated the optimal formulation parameters needed to achieve a high encapsulation of water-soluble drug into PLGA microspheres using emulsification techniques.