期刊
JOURNAL OF CONTROLLED RELEASE
卷 342, 期 -, 页码 189-200出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.12.038
关键词
Meloxicam; Hot-melt extrusion; Sustained drug delivery; Biocompatible polymer; Implant
资金
- Eli Lilly and Company
In this study, a polymeric implant that can sustain release meloxicam was developed for effective resolution of regional subacute inflammation and prevention of biofouling formation. The choice of polymer platform is crucial to continuous release of meloxicam, and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices.
ABSTR A C T For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(epsilon-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly (ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively. PCL allowed for sustained release of meloxicam over two weeks and was used as a carrier of meloxicam. Solid-state and image analyses indicated that the PCL matrices encapsulated meloxicam in crystalline clusters, which dissolved in aqueous medium and generated pores for subsequent drug release. The subcutaneously implanted meloxicam-loaded PCL matrices in rats showed pharmacokinetic profiles consistent with their in vitro release kinetics, where higher drug loading led to faster drug release. This study finds that the choice of polymer platform is crucial to continuous release of meloxicam and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices.
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