Multifunctional poly(β-amino ester) hydrogel microparticles in periodontal in situ forming drug delivery systems

In situ forming implants (ISIs) formed from poly(lactic-co-glycolic acid) (PLGA) have been commercialized for local drug delivery to treat periodontitis, but drug release from these bulk materials is typically subject to an initial burst. In addition, PLGA has inferior material properties for the dynamic mechanical environment of gingival tissue. In this work, poly(β-amino ester) (PBAE) hydrogel microparticles were incorporated into a PLGA matrix to provide several new functions: mechanical support, porosity, space-filling, and controlled co-delivery of antimicrobial and osteogenic drugs. First, the effects of PBAE microparticles on ISI architecture and material properties throughout degradation were investigated. Second, the influence of PBAE microparticles on drug release kinetics was quantified. Over a 15 d period, ISIs containing PBAE microparticles possessed greater porosity, ranging from 42-80%, compared to controls, which ranged from 24-54% (p < 0.001), and these ISIs also developed significantly greater accessible volume to simulated cell-sized spheres after 5 d or more of degradation (p < 0.001). PBAE-containing ISIs possessed a more uniform microarchitecture, which preserved mechanical resilience after cyclical loading (p < 0.001), and the materials swelled to fill the injected space, which significantly increased interfacial strength in an artificial periodontal pocket (p < 0.0001). PBAE microparticles eliminated the burst of freely-mixed simvastatin compared to 36% burst from controls (p < 0.0001), and high-dose doxycycline release was prolonged from 2 d to 7 d by pre-loading drug into the microparticles. PBAE-containing PLGA ISIs are more effective space-filling scaffolds and offer improved release kinetics compared to existing ISIs used to treat periodontitis.