The aim of this study was to develop biodegradable, photo-polymerizable in situ gel-forming systems prepared from a fumaric acid monoethyl ester (FAME) modified poly(lactide-co-glycolide) (PLGA) co-polymer. By reacting lactide and glycolide in the presence of stannous octoate as a catalyst and 2-ethyl,2-hydroxymethyl 1,3-propanediol as an initiator, hydroxyl terminated branched PLGA was synthesized. Afterwards, at room temperature hydroxyl terminated branched PLGA was reacted with fumaric acid monoethyl ester (FAME). N,N'-dicyclohexylcarbodiimide and triethylamine were used as a coupling agent and catalyst, respectively. The gel percentage, equilibrium mass swelling, degradation profile and polymerization kinetics of the hydrogels were investigated. All of the results were influenced by the amount of FAME modified PLGA co-polymer. Biocompatibility of the hydrogels was examined by using MTT cytotoxicity assay. According to the results, hydrogels are biocompatible and cell viability percentage depends on the amount of PLGA co-polymer. While the amount was 15% in hydrogel composition, cell viability was 100%, but after increasing the PLGA co-polymer amount to 30% the viability reduced to 78%.
A branched methacrylated poly(caprolactone-co-lactic acid) and methacrylated poly(tetramethylene ether glycol) (PTMG-IEM) resins were synthesized. 1 H-NMR spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) spectroscopy, and gel permeation chromatography confirmed the chemical structures of copolymers. The photoinitiated polymerization of formulation composed of various amounts of methacrylated poly(caprolactone-co-lactic acid), PTMG-IEM, poly(ethylene glycol) diacrylate, water, and photoinitiator were performed. The curing reactions were followed by photo-DSC (Differential scanning calorimetry). Gel fraction was calculated from the insoluble part and found as ≥93%. Swelling and contact angles were measured, and all increased with the increasing amount of PTMG-IEM in network formulations. In vitro degradation studies were performed at 37 C in phosphate-buffered saline (pH 7.4). Collagen-modified polymers were also prepared and introduced as a bioactive moiety to modify the polymer to enhance cell affinity. To compare the cell adhesion affinity to the polymer with and without collagen, cell growth experiments were performed. The results showed that collagen improves the cell adhesion onto the polymer surface. With the increasing amount of collagen, cell viability increases 86% (ECV304, p < 0.05) and 83% (3 T3, p < 0.05).Preparation of collagen-tethered PEGMA PEGMA (11 g) was poured into a three-necked 100 ml of a roundbottom flask equipped with a magnetic stirrer, a condenser and a nitrogen inlet. CDI (5.5 g) was dissolved in 50 ml of THF then added dropwise into the reaction mixture while mixing. The reaction mixture was kept at 40 C for 24 hr. G. BAYRAMOĞLU ET AL.wileyonlinelibrary.com/journal/pat Scheme 1. The synthesis of poly(caprolactone-co-lactic acid).Scheme 2. Synthesis of methacrylated poly(caprolactone-co-lactic acid).
Objective: It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment. Methods: We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA. Results: Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1β, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05). Conclusion: Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1β, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1β, and IL-6 with adenosinergic modulation may decrease seizure severity.
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