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In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth
Yan Xiong1, Zeping Yu1, Yun Lang1
1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Objective:
To study the degradation and basic fibroblast growth factor (bFGF) release activity of bFGF - poly(lactic-co-glycolic-acid) microsphere (bFGF-PLGA MS) under stress in vitro, including the static pressure and shearing force-simulating mechanical environment of the joint cavity.
Method:
First, bFGF-PLGA MSs were created. Meanwhile, two self-made experimental instruments (static pressure and shearing force loading instruments) were initially explored to provide stress-simulating mechanical environment of the joint cavity. Then, bFGF-PLGA MSs were loaded into the two instruments respectively, to study microsphere degradation and drug release experiments. In the static pressure loading experiment, normal atmospheric pressure loading (approximately 0.1 MPa), 0.35 MPa, and 4.0 MPa pressure loading and shaking flask oscillation groups were designed to study bFGF-PLGA MS degradation and bFGF release. In the shearing force loading experiment, a pulsating pump was used to give the experimental group an output of 1,000 mL/min and the control group an output of 10 mL/min to carry out bFGF-PLGA MS degradation and drug release experiments. Changes of bFGF-PLGA MSs, including microsphere morphology, quality, weight-average molecular weight of polymer, and microsphere degradation and bFGF release, were analyzed respectively.
Results:
In the static pressure loading experiment, bFGF-PLGA MSs at different pressure were stable initially. The trend of molecular weight change, quality loss, and bFGF release was consistent. Meanwhile, microsphere degradation and bFGF release rates in the 4.0 MPa pressure loading group were faster than those in the normal and 0.35 MPa pressure loading groups. It was the fastest in the shaking flask group, showing a statistically significant difference (P<0.0001). In the shearing force loading experiment, there were no distinctive differences in the rates of microsphere degradation and bFGF release between experimental and control group. Meanwhile, microsphere degradation and bFGF release rates by shaking flask oscillation were obviously faster than those by shearing force only (P<0.0001).
Conclusion:
There are significant effects on bFGF-PLGA MS degradation and bFGF release due to the interaction between extraction stress and time. Static pressure has a conspicuous influence on bFGF-PLGA MS degradation and release, especially at a pressure of 4.0 MPa. The shearing force has a slight effect on bFGF-PLGA MS degradation and drug release. On the contrary, shaking flask oscillation has a significantly distinctive effect.
Insights
Static pressure significantly impacts basic fibroblast growth factor (bFGF) release from poly(lactic-co-glycolic-acid) microspheres (bFGF-PLGA MS), with higher pressures accelerating degradation and release. Shearing force has minimal effect, while shaking flask oscillation significantly increases both processes.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Mechanical Engineering in Medicine
Background:
- Poly(lactic-co-glycolic-acid) microspheres (PLGA MS) are widely used for controlled drug delivery.
- Basic fibroblast growth factor (bFGF) is crucial for tissue regeneration.
- The mechanical environment of the joint cavity can influence the stability and release kinetics of intra-articular drug delivery systems.
Purpose of the Study:
- To investigate the in vitro degradation and bFGF release of bFGF-PLGA MS under simulated joint mechanical stresses.
- To evaluate the impact of static pressure and shearing force on bFGF-PLGA MS performance.
- To compare the effects of different mechanical stimuli on microsphere stability and drug release.
Main Methods:
- Fabrication of bFGF-PLGA MS.
- Development of custom instruments to apply static pressure (0.1, 0.35, 4.0 MPa) and shearing force (10 mL/min vs. 1000 mL/min).
- Analysis of microsphere morphology, molecular weight, degradation, and bFGF release under various mechanical conditions and shaking flask oscillation.
Main Results:
- Static pressure accelerated microsphere degradation and bFGF release, with a dose-dependent effect, particularly at 4.0 MPa.
- Shearing force showed no significant impact on microsphere degradation or bFGF release rates compared to control.
- Shaking flask oscillation led to significantly faster degradation and bFGF release compared to static pressure and shearing force alone.
Conclusions:
- Mechanical stress, particularly static pressure, significantly affects the degradation and bFGF release from bFGF-PLGA MS.
- High static pressure (4.0 MPa) markedly enhances microsphere degradation and drug release.
- Shearing force has a minimal effect, while dynamic agitation (shaking flask) demonstrates a substantial influence on bFGF-PLGA MS performance.
