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. 2013 Nov;34(34):8835-42.
doi: 10.1016/j.biomaterials.2013.07.093. Epub 2013 Aug 12.

Design of a multiple drug delivery system directed at periodontitis

Sharath C Sundararaj  1 , Mark V Thomas, Rebecca Peyyala, Thomas D Dziubla, David A Puleo
Affiliations

Design of a multiple drug delivery system directed at periodontitis

Sharath C Sundararaj et al. Biomaterials. 2013 Nov.

Abstract

Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions.

Keywords: Controlled drug release; Drug delivery; Drug release; Periodontium; Sequential drug release.

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Figures

Figure 1
Figure 1
Proposed sequential drug delivery based on the pathogenesis of periodontal disease.
Figure 2
Figure 2
Schematic representation of how multilayered CAPP devices were fabricated. (A) 7-layer device with one blank layer between drug layers. (B) 10-layer device with two blank layers between drug layers. (C) 10-layer device with PSA layer between the blank layers. Note: Illustration is not to scale.
Figure 2
Figure 2
Schematic representation of how multilayered CAPP devices were fabricated. (A) 7-layer device with one blank layer between drug layers. (B) 10-layer device with two blank layers between drug layers. (C) 10-layer device with PSA layer between the blank layers. Note: Illustration is not to scale.
Figure 2
Figure 2
Schematic representation of how multilayered CAPP devices were fabricated. (A) 7-layer device with one blank layer between drug layers. (B) 10-layer device with two blank layers between drug layers. (C) 10-layer device with PSA layer between the blank layers. Note: Illustration is not to scale.
Figure 3
Figure 3
Mass loss profiles for: (A) 7-layered blank and drug-loaded CAPP devices; (B) Drug-loaded devices with one blank layer, two blank layers, or two blank layers along with PSA between the drug layers. Data are mean ± standard deviation (n=3).
Figure 3
Figure 3
Mass loss profiles for: (A) 7-layered blank and drug-loaded CAPP devices; (B) Drug-loaded devices with one blank layer, two blank layers, or two blank layers along with PSA between the drug layers. Data are mean ± standard deviation (n=3).
Figure 4
Figure 4
Fractional instantaneous release profiles of four drugs from: (A) 7-layer devices with single blank layers; (B) 10-layer devices with two blank layers; and (C) 10-layer devices with double blank layers plus PSA. Data are mean ± standard deviation (n=3).
Figure 4
Figure 4
Fractional instantaneous release profiles of four drugs from: (A) 7-layer devices with single blank layers; (B) 10-layer devices with two blank layers; and (C) 10-layer devices with double blank layers plus PSA. Data are mean ± standard deviation (n=3).
Figure 4
Figure 4
Fractional instantaneous release profiles of four drugs from: (A) 7-layer devices with single blank layers; (B) 10-layer devices with two blank layers; and (C) 10-layer devices with double blank layers plus PSA. Data are mean ± standard deviation (n=3).
Figure 5
Figure 5
Cumulative drug release from double blank layer devices along with mathematical modeling.
Figure 6
Figure 6
Percentage of bioactivity retained by metronidazole and ketoprofen released from CAPP films. Data are mean ± standard deviation (n=3).
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