Manufacturing Doxycycline and Metal Ion Loaded Polymethylmethacrylate Microspheres.

Objectives: To test the feasibility of incorporating doxycycline and metal ions into PMMA microspheres at 50um size; to evaluate the drug loading efficiency and drug release profiles.
Methods: 4 groups were tested: 1. Pure PMMA-microspheres (25% weight); 2. PMMA-microspheres containing 15% doxycycline; 3. PMMA-containing 5% metal salt; 4. PMMA-microspheres containing 5% metal salt and 15% doxycycline. Doxycycline and metal salt loading and drug release profiles were analyzed in a HPLC and ICP-MS respectively. All microspheres were observed under a light microscope at 100x magnification during manufacturing for spherical shape, drug encapsulation and a targeted 50um diameter. The formulation containing 5% metal salt + 15 % doxycycline was analyzed in a Malvern mastersizer instrument.
Results: The lead formulation of PMMA containing theoretically maximal amounts of 5% metal salt + 15% doxycycline showed 8.3 ± 0.64 % doxycycline drug loading to give a 55% encapsulation efficiency; and a 0.36 ± 0.03 % metal salt loading for a 7.2 % encapsulation efficiency. Similarly, PMMA/15%doxycycline alone showed 8.1 ± 0.88 % doxycycline drug loading and 54% encapsulation efficiency. PMMA/5% metal salt alone presented 0.46 ± 0.07 % drug loading and 9.3% encapsulation efficiency. The lead formulation (PMMA/dox15%/metal5%) showed continued metal salt and doxycycline release up to 15 days in a biphasic media. The method used successfully produced microspheres with a median diameter close to 50um.
Conclusions: PMMA microspheres containing both doxycycline and metal salt were successfully manufactured with a target diameter of 50um. The final encapsulation efficiencies for the two drugs (approximately 55% doxycycline and 7% metal salt) provided suitable microspheres for incorporation into orthopaedic and dental materials.