In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere

Drug Design, Development and Therapy, Jan 2016

In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere Yan Xiong,1 Zeping Yu,1 Yun Lang,1 Juanyu Hu,1 Hong Li,2 Yonggang Yan,2 Chongqi Tu,1 Tianfu Yang,1 Yueming Song,1 Hong Duan,1 Fuxing Pei1 1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Laboratory of Biomechanical Engineering, 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

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In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere

Drug Design, Development and Therapy in vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor - poly(lactic-co-glycolic-acid) microsphere Yan Xiong 1 Zeping Yu 1 Yun lang 1 Juanyu hu 1 hong li 0 Yonggang Yan 0 chongqi Tu 1 Tianfu Yang 1 Yueming song 1 hong Duan 1 Fuxing Pei 1 0 l aboratory of Biomechanical engineering, sichuan University , c hengdu, s ichuan, People's r epublic of china 1 Department of Orthopedics, West china hospital, sichuan University , c hengdu, s ichuan, People's r epublic of china 8 1 0 2 - l u J - 2 1 n o 9 1 1 . 9 5 . 2 3 . 3 1 2 y b / m o c . s s e r p e v o ./dwww l.yeon PowerdbyTCPDF(ww.tcpdf.org) - 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. Keywords: microsphere, basic fibroblast growth factor, bFGF, poly(lactic-co-glycolic-acid), PLGA, stress, drug release Introduction Basic fibroblast growth factor (bFGF) is a member of the FGF family of proteins, which has been studied in embryonic development, nerve nutrition and regeneration, bone and muscle growth, blood vessel formation, wound healing, and tumor growth 8 1 0 2 l u J 2 1 n o 9 1 1 . 9 5 . 2 3 . 3 1 2 y b / m o c . s s e r p e v o and differentiation.1–7 However, because of its instability at high temperatures and in acidic environments its short half-life of 3–5 minutes in vivo, bFGF cannot meet clinical application criteria satisfactorily. Poly(lactic-co-glycolicacid) (PLGA), which is a biodegradable material, has been widely used in pharmaceutical industry as a carrier to load drugs and lengthen sustained release. Over the past few decades, PLGA microspheres (MSs), formulated into different devices for loading a variety of drugs or reagents such as vaccines, antibiotics, peptides, proteins, and micromolecules, have been used to treat disease and promote tissue regeneration and repair.8–10 They can also be used for cartilage injury regeneration and repair, as the cartilage lacks good self-repairing ability.11–15 Generally, because of low self-repair capability, articular cartilage injury is a common and severe disease that seriously affects physical function and quality of life.11 The current methods of repair include the application of exog.//:sdwww l.yseonu setnuoduiessg.1r2o–1w6TthhefabcFtoGrFs,-PaLsGhAavMeSbeceonulrdepboeritnejdecitnedpirnetvoiothues ttph lan joint cavity to promote cartilage defect healing. However, o rom rse the complex environment of joint cavity, especia (...truncated)


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Yan Xiong, Zeping Yu, Yun Lang, Juanyu Hu, Hong Li, Yonggang Yan, Chongqi Tu, Tianfu Yang, Yueming Song, Hong Duan, Fuxing Pei. In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere, Drug Design, Development and Therapy, 2016, pp. 431-440, DOI: 10.2147/DDDT.S93554