TY - JOUR
T1 - Development and characterization of tetracycline-poly(lactide/glycolide) films for the treatment of periodontitis
AU - Agarwal, Rajesh K.
AU - Robinson, Dennis H.
AU - Maze, Glenn I.
AU - Reinhardt, Richard A.
PY - 1993/2
Y1 - 1993/2
N2 - 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 (r2 ≥ 0.96) and drug loading (r2 ≥ 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.
AB - 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 (r2 ≥ 0.96) and drug loading (r2 ≥ 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.
KW - Biodegradable films
KW - Periodontitis
KW - Poly(lactide/glycolide)
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U2 - 10.1016/0168-3659(93)90039-8
DO - 10.1016/0168-3659(93)90039-8
M3 - Article
AN - SCOPUS:0027506867
SN - 0168-3659
VL - 23
SP - 137
EP - 146
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -