L. Hurley et Br. Andersen, Biodegradable implants from poly-(alpha-hydroxy acid) polymers for isoniazid delivery, INT J TUBE, 3(11), 1999, pp. 1015-1024
Citations number
14
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
SETTING: In vitro and in vivo study of an isoniazid (INH) drug delivery sys
tem.
OBJECTIVE: To develop a system for the treatment of tuberculosis using a su
bcutaneous polymer implant with a large drug load released slowly over a lo
ng period. INH delivery by biodegradable poly-(alpha-hydroxy acid) polymers
was evaluated using ground polymer and compression molded implants.
DESIGN: Rate of drug release and structural stability of the implant in an
aqueous environment were measured, as were in vivo evaluations of the durat
ion of measurable levels of INH in serum and urine.
RESULTS: Factors that influenced the suitability of an implant in an in vit
ro system included polymer molecular weight and crystallinity, polymer and
drug particle size, drug loading dose, and press temperature and pressure.
The implant characteristics that most closely approached optimal conditions
include a polymer of 100% L-lactide with low intrinsic viscosity, polymer
particle size <75 mu, and INH particle = 126-180 mu, INH loading dose not t
o exceed 46%, and press conditions of 70 degrees C and 345 000 kPa. Studies
of subcutaneous implants in rabbits and baboons show that INH is released
from the implant for 15 to 26 weeks.
CONCLUSIONS: An INH-containing polymer was developed that was structurally
stable in an aqueous environment and that released INH over a period of at
least 15 weeks. Studies with infected animals will be necessary to determin
e the dose required for prophylaxis and treatment of active disease.