Sequential Drug Delivery System Designed as a Potential Periodontitis Treatment

Objective: The main aim of this research was to develop a multiple drug delivery device that will release four drugs in an appropriate sequence to treat different stages of periodontitis.

Method: Drug-loaded and blank cellulose acetate phthalate - Pluronic F-127 (CAPP) films were made using a solvent evaporation technique. The multiple drug delivery device was fabricated by attaching blank and drug-loaded films in the desired order within a polystyrene backing. The drug loaded layers include antibiotic (metronidazole), anti-inflammatory (ketoprofen), anti-resorptive/antibiotic (doxycycline), and osteogenic (simvastatin) drugs. Drug delivery devices were characterized by SEM imaging, in vitro drug release, and bioactivity studies.

Result: The in vitro studies showed that drug release from the CAPP films occurred in a zero-order (time-independent) manner. Release of metronidazole, ketoprofen, doxycycline, and simvastatin in the required temporal sequence was achieved. This temporal sequence was designed based on the pathophysiologic stages of periodontitis. The amount of drugs released was comparable to the amount of drug loaded in the CAPP films. The bioactivity studies that were conducted on the release supernatants also showed that the drug released from the CAPP device was in bioactive form.

Conclusion: The CAPP devices degraded by surface erosion and therefore were capable of releasing different drugs in a predetermined order. The amount of drug loaded/released can be tuned according to a particular drug and its dosage requirement. The sequential release of multiple drugs can be used to treat the bacterial infection, inflammatory, and bone resorption stages of periodontitis and then subsequently help in regeneration of the alveolar bone. Ongoing work involves fabrication of these multilayer CAPP films for in vivo studies.