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pubmed:abstractText |
Bisphosphonate drugs alter the balance of bone resorption and formation, leading to a net increase in bone density. Therefore, these drugs are commonly used to treat osteoporosis or as an adjunct to cancer chemotherapy. Local delivery of bisphosphonates, such as alendronate, from polymeric films has the potential to improve efficacy and decrease side-effects common to oral bisphosphonate therapy. Alendronate was effectively encapsulated in film formulations composed of poly(lactic-co-glycolic acid) (PLGA) blended with poly(DL-lactic acid)-block-methoxy poly(ethylene glycol) (diblock co-polymer) and the films were characterized for elasticity, swelling, thermal and drug-release properties. Increasing the proportion of diblock co-polymer in the formulation decreased the glass transition temperature of PLGA, allowing for improved handling via increases in film elasticity. Immersion in aqueous media caused a rapid stiffening and swelling of the films. The inclusion of diblock co-polymer increased the rate of drug release from the films over a 3-week period. Drug-loaded polymeric films containing 0.25% alendronate increased osteoblast viability after 4 days compared to polymer alone. After 5 weeks, there was a significant increase in alkaline phosphatase activity and calcium nodule formation in osteoblasts grown on films containing 1.25% alendronate in 5% diblock co-polymer in PLGA.
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