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Modified Cyclodextrin Microparticles to Improve PMMA Drug Delivery Without Mechanical Loss
Chao-Yi Lu1, Derek C Church2, Greg D Learn1
1Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Abstract:
Antibiotic-loaded poly(methyl methacrylate) (PMMA) cement is commonly used as a local delivery system to treat and prevent orthopedic infections associated with arthroplasties in load-bearing applications. However, these delivery systems are inefficient as release rate sharply declines to subinhibitory levels. Prior studies have shown that by adding in drug-filled cyclodextrin (CD) microparticles into PMMA cement, a more consistent release is observed, and antibiotic refilling through simulated implantation can be achieved. However, the mechanical strengths of PMMA is reduced. In order to decrease the mechanical loss, modified CD microparticles (PMMA-CD) are synthesized that contain covalently appended PMMA chains. The compressive strengths, handling characteristics, and refilling ability of PMMA cement with PMMA-CD are evaluated. Specifically, up to a 13.7% increase in compressive strength is observed when unmodified CD is substituted with PMMA-CD in PMMA samples with 10 wt% CD microparticles. Additionally, a 13.3% increase in working time, a 7.5% decrease in maximum polymerization temperature, and up to a 32.1% increase in amount of drug refilled are observed with the addition of 10 wt% CD PMMA-CD into PMMA in comparison to plain PMMA without CD microparticles.
Insights
Modified cyclodextrin microparticles improve poly(methyl methacrylate) bone cement for orthopedic infections. This enhances drug delivery and mechanical strength, offering a better solution for preventing implant-associated infections.
Area of Science:
- Biomaterials Science
- Orthopedic Surgery
- Drug Delivery Systems
Background:
- Poly(methyl methacrylate) (PMMA) cement is used for local antibiotic delivery in orthopedic infections.
- Current PMMA systems show inefficient drug release, declining to subinhibitory levels.
- Incorporating drug-filled cyclodextrin (CD) microparticles improves release consistency but reduces mechanical strength.
Purpose of the Study:
- To synthesize and evaluate modified cyclodextrin (PMMA-CD) microparticles.
- To assess the impact of PMMA-CD on the mechanical properties and drug delivery of PMMA bone cement.
- To investigate the refilling capability of PMMA cement containing PMMA-CD.
Main Methods:
- Synthesis of PMMA-CD microparticles with covalently appended PMMA chains.
- Evaluation of compressive strength, handling characteristics (working time, polymerization temperature), and drug refilling ability.
- Comparison of PMMA cement with PMMA-CD against plain PMMA and PMMA with unmodified CD.
Main Results:
- PMMA cement with 10 wt% PMMA-CD showed a 13.7% increase in compressive strength compared to unmodified CD.
- Working time increased by 13.3%, and maximum polymerization temperature decreased by 7.5%.
- Drug refilling amount increased by up to 32.1% with PMMA-CD compared to plain PMMA.
Conclusions:
- PMMA-CD microparticles mitigate the mechanical strength reduction typically seen with CD incorporation in PMMA.
- The modified microparticles enhance drug delivery consistency and refilling efficiency.
- PMMA-CD represents a promising advancement for antibiotic delivery in orthopedic applications, improving both mechanical integrity and therapeutic efficacy.
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