ABSTRACT
@#【Objective】To form a new PTMAc- PEG- PTMAc triblock（PPP）copolymerhydrogel and to evaluate its sustained released performance and antiproliferative effects as an ocular drug carrier of Pirfenidone（PFD）【Methods】One type triblockcopolymers PPP hydrogel was chosen. The morphology of the material was evaluated by scanning electron microscopy（SEM）. The swelling properties of the PPP hydrogel was analyzed in PBS solution（37 ℃ ，pH 7.4）. The in vitro drug release of the pirfenidone loaded hydrogels were evaluated with non-dialysis method and the curves of drug release were drawed. We evaluated the adhesion，survival of human Tenon′s capsule fibroblasts（HTF）around hydrogels. The cell cytotoxicity of hydrogels and antiproliferative effects were evaluated through CCK-8 assay.【Results】The hydrogel has stable gelation conditions. The swelling rate decreased by increasing hydrogel concentration.The SEM images indicated the fibrous and porous structure. We also observed that the encapsulated pirfenidone were sustained released from hydrogels with an initial burst release at early stage（within 4 d）and then the release rate were declined for all hydrogels during the following 14 d. The PPP hydrogel can inhibit cell adhesion. The cell viability in hydrogels at four time point（24，48，72 and 96 h）were 85.7% ，93.0% ，82.0% ，81.6%. The inhibition rate of drug loaded hydrogel with two drug concentration（1 mg/mL or 2 mg/mL）are 25.8%，21.8%，55.4%，25.6%；44.6%，35.9%，55.5%，31.4%. While that of drug solution are 28.9% ，29.7% ，7.8% ，7.7%. The suppressive effects of the PFD loaded hydrogels on HTF proliferation followed a dose-dependent fashion and time-dependent fashion.【Conclusions】Such biocompatible copolymers hydrogel can be effectively used as an drug sustain released system. It can induce significant inhibition of HTF proliferation. With equal amount of drug，the inhibition effect of drug loaded gel was longer than that of drug solution.
ABSTRACT
<p><b>OBJECTIVE</b>To prepare a platinum microcoil coated with polymers and vascular endothelial growth factor (VEGF), and evaluate its surface characteristics and property of sustained VEGF release.</p><p><b>METHODS</b>The surface of the platinum microcoils (GDC) were modified by coating P(DLLA-co-TMC) copolymer and immobilizing heparin on the surface of GDC. VEGF was then loaded onto the surface of GDC and the controlled release of VEGF within GDC was achieved. The morphology was observed by scanning electron microscope, and the sustained release of VEGF was evaluated by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Platinum coils were prepared by successive deposition of P(DLLA-co-TMC) copolymer and anionic heparin, and VEGF was immobilized through affinity interaction with heparin. The accumulative release of VEGF increased obviously during the entire testing period without burst release.</p><p><b>CONCLUSION</b>The use of P(DLLA-co-TMC) copolymer allows immobilization of VEGF on the platinum coils for controlled VEGF release, and improves the biological property of the coils.</p>
Subject(s)
Coated Materials, Biocompatible , Chemistry , Delayed-Action Preparations , Pharmacology , Platinum , Chemistry , Polymers , Chemistry , Vascular Endothelial Growth Factor A , PharmacologyABSTRACT
<p><b>BACKGROUND</b>Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-beta1 (TGF-beta1) to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-beta1 delivery and the effect of released TGF-beta1 on the chondrogenic potential of chondrocytes.</p><p><b>METHODS</b>Chitosan scaffolds and chitosan microspheres loaded with TGF-beta1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-beta1 microspheres and incubated in vitro for 3 weeks. Histological examination and type II collagen immunohistochemical staining was performed to evaluate the effects of released TGF-beta1 on cell adhesivity, proliferation and synthesis of the extracellular matrix.</p><p><b>RESULTS</b>TGF-beta1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF-beta1 was high (90.1%). During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-beta1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-beta1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group (32.7% +/- 10.4%) was significantly lower than that in the controlled TGF-beta1 release group (92.4% +/- 4.8%, P < 0.05). Both the proliferation rate and production of collagen type II in the transforming growth factor-beta1 microsphere incorporated scaffolds were significantly higher than those in the scaffolds without microspheres, indicating that the activity of TGF-beta1 was retained during microsphere fabrication and after growth factor release.</p><p><b>CONCLUSION</b>Chitosan microspheres can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor can augment chondrocytes proliferation and synthesis of extracellular matrix. Chitosan scaffolds incorporated with chitosan microspheres loaded with TGF-beta1 possess a promising potential to be applied for controlled cytokine delivery and cartilage tissue engineering.</p>