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

Abstract

ObjectiveTo 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.MethodFirst, 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.ResultsIn 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).ConclusionThere 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.

Electrospun PLGA Nanofiber Scaffolds Release Ibuprofen Faster and Degrade Slower After In Vivo Implantation

“…In this work, we demonstrate that in vivo implantation of these scaffolds produces a distinctly different drug release profile and degradation properties versus in vitro incubation in PBS. Furthermore, whereas prior studies found faster release of biofactors with faster degradation, 44, 45 our study demonstrated an inverse relationship: the in vivo environment was associated with a slower polymer degradation, but a faster drug release.…”

“…There have been other reports that modifications to in vitro environment (such as change in pH, 17, 45 ionic strength, 17 and mechanical stress 44 ) as well as scaffold properties (such as scaffold shape, 23 composition, 35 and drug/biofactor 39 ) can alter the release kinetics and polymer degradation rate. In this work, we demonstrate that in vivo implantation of these scaffolds produces a distinctly different drug release profile and degradation properties versus in vitro incubation in PBS.…”

Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles

“…In particular, polyesters based therapeutics gain success in improving chemotherapeutic efficacy, both in vitro and in vivo, and anti-inflammatory response for treatment of cancer (Hu and Zhang 2012) and inflammatory diseases (Danhier et al 2012) respectively in various administration routes. Bioinert and biodegradable PLA and PLGA drug carrier materials hold outstanding advantages, including (i) sustainable delivery (Mansor et al 2018), (ii) proper control of drug release kinetics (iii) diminished fluctuations of blood drug concentrations (Makadia and Siegel 2011), (iv) augmented cellular uptake of NPs via endocytosis (Bi et al 2016;Priemel et al 2018), (v) enhanced stability (Xiong et al 2016), (vi) optimal clinical utility (Lü et al 2009) and (vii) improved medication adherence (Liu et al 2006).…”

Antitumor Efficacy and Toxicity of 5-Fluorouracil-Loaded Poly(Lactide Co-glycolide) Pellets

“…The finding that in vivo release was faster than in vitro release was entirely expected and has been demonstrated in previously published work involving independent formulations. [18, 19] Enzymes [20, 21] , biological surfactants [22] and mechanical forces [23] are likely responsible for enhancing 5-FU release rate in vivo . Lysozymes [20] , esterases, and lipases [21] have shown the ability to catalyze the hydrolysis of PLGA in vitro .…”