Development and characterization of tetracycline-poly(lactide/glycolide) films for the treatment of periodontitis

Abstract

Local delivery of antibiotics has been shown to be effective in reducing periodontopathic micro-organisms. The objective of this research was to develop a biodegradable, poly( d, l-lactide/glycolide), 85:15, (PLGA) film that was capable of delivering therapeutic concentrations of tetracycline HCl for a duration of two weeks into the intra-crevicular fluid within the inflamed periodontal pocket. Films (10 × 2 × 0.5 mm) containing varying amounts (10 to 25% w/w) of tetracycline HCl were prepared by film casting a dispersion of the drug in a solution of PLGA dissolved in methylene chloride. Differential dissolution studies were performed in buffer, pH 7.3, at 37°C. Both the rate and percent of drug released increased as drug loading and dissolution media pH increased. However, complete release of drug from the films was not obtained as 83.1 ± 7.0 μg of tetracycline HCl per mg of PLGA was retained for all drug loadings. Linear relationships obtained for graphs of the percent released versus both the square root of time ( r 2 ≥ 0.96) and drug loading ( r 2 ≥ 0.99) indicated a matrix-controlled release from a porous, granular, monolithic system. Preliminary results from a clinical study with 8 periodontal, maintenance patients indicate that films containing 25% w/w tetracycline HCl were effective in decreasing the bacterial count in the intra-crevicular fluid and demonstrated a significant ( p ⩽ 0.01) microbial inhibition for two weeks over the control placebo film. The decrease in tetracycline HCl concentration in the gingival fluid was approximated by a first order relationship with the tetracycline HCl disappearance rate constant of 0.19 days −1.