5'-DMT-dG(iBu)-Suc-CPG; 500 Å

Osteoarthritis (OA) is a disease of articular cartilage degradation and inflammation of the joint capsule. Combining anti-inflammatory therapy with nutritional supplement is an effective means for the treatment of OA. In this study, we prepared gelatin (Gel)-glucosamine hydrochloride (GH) mixed crosslinked-cyclodextrin metal-organic framework (G-GH/CL-CD-MOF) composite hydrogel. Polyethylene glycol diglycidyl ether was the crosslinking agent of GH and Gel to solve the problem of poor mechanical properties and water solubility at 37 °C. CL-CD-MOF was fabricated through a simple one-step chemical reaction to crosslink the hydrophilic hydroxyl groups in CD-MOF with diphenyl carbonate. Electron microscopy and x-ray diffraction analysis of CL-CD-MOF showed perfect porous morphology with a chaotic internal structure. CL-CD-MOF@IBU was prepared by immersing CL-CD-MOF in high-concentration ibuprofen (IBU) solution. CL-CD-MOF@IBU was uniformly dispersed in Gel and GH mixed solution to prepare G-GH/CL-CD-MOF@IBU composite hydrogel long-term sustained drug delivery system. The compression curve of G-GH/CL-CD-MOF composite hydrogel showed a non-linear elastic behavior. The cyclic loading-unloading compression showed that the shape of the G-GH/CL-CD-MOF composite hydrogel can be kept intact under 50% strain. On the day 14, the G-GH/CL-CD-MOF@IBU composite hydrogel was degraded by 87.1%, 61% of IBU was released. G-GH/CL-CD-MOF@IBU exhibited good biocompatibility during co-culture with MC3T3-E1 cells. Briefly, the certain mechanical properties, sustained drug release behavior, and good biocompatibility of G-GH/CL-CD-MOF@IBU composite hydrogel showed that it has potential application in OA treatment of long-term sustained nutritional supplement and anti-inflammatory synchronously.

The aim of this study is to assess the toxicity of ibuprofen (IBU) and propranolol (PRO) drugs usingGammarus pulex as a model organism. Firstly, the 96 h LC50 values of IBU and PRO were determined and then three sublethal concentrations of the drugs were exposed to G. pulex. The activities of superoxide dismutase (SOD), catalase (CAT) and acetylcholinesterase (AChE) were evaluated. SOD activity decreased in G. pulex exposed to IBU and PRO compared to control. In all groups exposed to IBU, CAT activity increased at different concentrations at 24 and 96 h. In the groups exposed to different PRO concentrations, CAT activities increased after 24 h compared to the control group (p < 0.05). AChE activities increased in all application groups exposed to IBU for 96 hours (p < 0.05). In conclusion, exposure to IBU and PRO resulted in increased oxidative damage. PRO has been found to cause neurotoxicity.

Ibuprofen (IBU) is an efficacious over-the-counter analgesic/antipyretic with adverse event (AE) rates comparable to placebo. IBU sodium (IBU(Na)) is a newer, more soluble form that is absorbed faster than standard IBU, leading to more rapid analgesia. Although its safety and tolerability are expected to be comparable to standard IBU, this has not yet been reported. Pooled analysis comparing the safety of single-dose IBU(Na) (512 mg; equivalent to 400 mg IBU free acid; n = 362) with standard IBU tablets (400 mg; n = 342) and placebo (n = 187) across five Phase III, randomized, placebo-controlled, double-blind studies evaluating IBU(Na) for treatment of postoperative dental pain, tension-type headache, or fever. Treatment-emergent AEs (TEAEs) occurred in 5% of cases in the IBU(Na) group (25 events), 6.4% of cases in the standard IBU group (41 events), and 10.2% of cases in the placebo group (31 events). The most frequent TEAEs were in the following Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes: gastrointestinal disorders (2.8, 3.2, and 5.9% for IBU(Na), standard IBU, and placebo, respectively), nervous system disorders (1.4, 3.5, and 3.7% for IBU(Na), standard IBU, and placebo, respectively), and general disorders and administration-site conditions (1.1, 1.5, and 2.1% for IBU(Na), standard IBU, and placebo, respectively). Nausea was the most common TEAE (2.5, 2.6, and 5.9% for IBU(Na), standard IBU, and placebo, respectively). Only two AEs were considered related to treatment: pruritus (n = 1, IBU(Na)) and nausea (n = 1, placebo). Of those subjects reporting ≥ 1 TEAE, 44.4, 36.4, and 89.5% of subjects in the IBU(Na), standard IBU, and placebo groups, respectively, received rescue medication. IBU(Na) has a favorable safety profile comparable to those of standard IBU tablets and placebo in single-dose studies evaluating analgesic or antipyretic efficacy. ClinicalTrials.gov Registry Numbers: Dental pain studies: NCT01098747 and NCT01216163; headache studies: NCT01077973 and NCT01362491; pyresis study: NCT01035346.