Prevention of postsurgical tissue adhesion by anti‐inflammatory drug‐loaded pluronic mixtures with sol–gel transition behavior

Abstract

Sol-gel transition temperature-controllable Pluronic F127/F68 mixtures including mildly crosslinked alginate and nonsteroidal anti-inflammatory drug (ibuprofen) were prepared to evaluate their potential as tissue adhesion barrier gels. The sol-gel transition temperatures of the Pluronic mixtures could be controlled by adjusting F127/F68 ratio and polymer concentration. The mildly crosslinked alginate with still flow property provided the residence stability of Pluronic mixture gels in the body. Ibuprofen was loaded in Pluronic mixtures to reduce inflammatory response in the body and, thus, to prevent tissue adhesion. The gelation temperatures of the Pluronic mixtures were not affected by the alginate but lowered by the addition of ibuprofen. The in vitro drug release behavior and in vivo peritoneal tissue adhesion of the Pluronic mixtures with the sol-gel transition just below body temperatures were investigated. The drug release behavior from the ibuprofen (1 wt%)-loaded Pluronic mixture gels at 37 degrees C was examined using a membrane-less dissolution model. The drug in the mixture gels was released continuously up to about 45-65% of the total loading amount during the first 7 days. For in vivo evaluation of tissue anti-adhesion potential, the Pluronic mixtures with/without drug were coated on the peritoneal wall defects of rats and their tissue adhesion extents and tissue reactions (inflammatory response, granulation tissue formation, and toxicity in organs) were compared. It was observed that ibuprofen has a positive effect for the peritoneal tissue anti-adhesion. The Pluronic F127/F68/alginate/ibuprofen mixture gel (25 wt% of F127/F68 [7/3], 1 wt% ibuprofen) was highly effective for the prevention of peritoneal tissue adhesion and showed a relatively low inflammatory response and non-toxicity, and thus can be a good candidate material as a coatable or injectable tissue adhesion barrier gel.

The effectiveness of poloxamer 407-based new anti-adhesive material in a laminectomy model in rats

“…Poloxamer, a substance composed of nonionic triblock copolymers of the central hydrophobic polypropylene and side hydrophilic polyethylene, is extensively used as a surfactant owing to its amphiphilic feature. Oh et al [33] reported that poloxamer is a good anti-adhesive agent playing the barrier's role appropriately, because it showed fairly good anti-adhesion effects, had small inflammatory reaction and non-toxicity within the body in a study using the peritoneum adhesion model in rats. Reigel et al [34] also said that the substance had about 50% of anti-adhesion effects in an experimental study using the laminectomy model in rabbits, affirming that poloxamer is a useful anti-adhesive agent in spine surgery.…”

The Effects of Barrier Materials on Reduction of Pericardial Adhesion Formation in Rabbits: A Comparative Study of a Hyaluronan-Based Solution and a Temperature Sensitive Poloxamer Solution/Gel Material

“…Some of them need additional fixations to prevent migration. Some of them are very difficult to reposition once placed [7,21,22]. Moreover, it is difficult to cover actively moving 3-dimensional structures such as the heart, graft vessels, and coronary bypass grafts with film type barriers.…”

“…However, they flow to the dependant portion and can be drained too early by a drainage catheter before they can prevent adhesion formation [22]. Thus, the viscosity of the solution type barrier is an important factor in the clinical field.…”

Celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting ERK1/2 and SMAD2/3 phosphorylation

“…The cells were seeded onto 90-mm tissue culture dishes and grown to 80% confluence, then used for ERK1/2 (Cell Signaling, USA), SMAD2/3 (Cell Signaling), collagen (Santa Cruz Biotechnology, Santa Cruz, CA, USA), and cell proliferation assays. 4 /ml) were seeded in 96-well culture plates. NIH/3T3 cells, with and without stimulation by FGF-2, were treated with increasing Celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting ERK1/2 and SMAD2/3 phosphorylation concentrations of celecoxib.…”

“…Certain selective and nonselective cyclooxygenase-2 enzyme (COX-2) inhibitors have been shown to inhibit adhesion formation, but have rarely been applied clinically due to their limited effect (4)(5)(6)(7)(8)(9)(10). Celecoxib, a selective COX-2 inhibitor, has been shown to produce a maximal reduction in intra-abdominal adhesion formation in comparison to rofecoxib and nonselective COX-2 inhibitors, and therefore provides a promising therapy for all types of adhesions (11,12).…”