Thermosensitive Polymer Blend Composed of Poloxamer 407, Poloxamer 188 and Polycarbophil for the Use as Mucoadhesive In Situ Gel

Abstract

Herein, thermosensitive blends of poloxamer 407 (P407)/poloxamer 188 (P188)/polycarbophil (PCB) were developed in terms of maximized content of PCB (a mucoadhesive polymer) and desired temperature-dependent rheological properties of the blends as in situ gelling matrices. Maximizing PCB content while achieving the preferable rheological characteristics was accomplished through the Box–Behnken design. The quantitative effect of the polymer composition in the blends on the thermosensitive characteristics was evaluated using the fitted design model and the corresponding surface plots. The optimized P407/P188/PCB blend (OPT) was the mixture of 20.000, 7.349 and 0.595% (w/w) of P407, P188, and PCB, respectively. The thermosensitive micellization of OPT was investigated using differential scanning calorimetry which revealed an overlapping double endothermic peak caused by the temperature-induced micellization of pure micelles in co-existence with the micelles with attached PCB. Mixing PCB with the P407/P188 matrix promoted a more intense mucoadhesion of the blend. After incorporating metronidazole, a model hydrophilic drug, into OPT, the temperature-dependent characteristics of the hydrogel did not change. Metronidazole release from OPT was sustained by an anomalous mechanism. This optimal ternary hydrogel benefiting from thermosensitive gelling and mucoadhesive matrix might be used as a viable platform for mucoadhesive in situ gelling drug delivery.

Investigating the Targeting Power to Brain Tissues of Intranasal Rasagiline Mesylate-Loaded Transferosomal In Situ Gel for Efficient Treatment of Parkinson’s Disease

“…As previously reported by Yuan et al, who explained the idea that Pluronics with high hydrophobic PPO (such as Pluronic ® F-127) proportion had low sol-to-gel transition temperature, while those composed of high hydrophilic PEO (such as Pluronic ® F-68) proportion demonstrated higher gelation temperatures [ 93 ]. This confirms the result that the incorporation of Pluronic ® F-68 having higher PEO/PPO ratio compared with Pluronic ® F-127 led to the elevation of gelation temperature [ 52 ]. By checking the results of the sol-to-gel transition time, it was obvious that the obtained values were around 15 s.…”

“…Moreover, it was noticed that elevating the concentration of Pluronic ® F-68 from 5 to 10% w / v led to a corresponding increase in the sol-to-gel transition temperature from 36.2 ± 0.282 °C to 40.1 ± 1.69 °C. This observation might be attributed to the presence of a higher PEO/PPO ratio in the structure of Pluronic ® F-68 compared with Pluronic ® F-127 [ 52 ]. As previously reported by Yuan et al, who explained the idea that Pluronics with high hydrophobic PPO (such as Pluronic ® F-127) proportion had low sol-to-gel transition temperature, while those composed of high hydrophilic PEO (such as Pluronic ® F-68) proportion demonstrated higher gelation temperatures [ 93 ].…”

“…This was carried out by placing the gel sample (5 mL) in a shearing jig and testing them at a frequency of 1 Hz and amplitude gamma of 1%. A gradual increase in temperature from 25 to 37 °C was made with an elevation rate of 2 °C/min [ 52 ]. Complex viscosity (ɳ * ) was plotted against temperature (T) to detect the ability of the tested samples to transform into a gel at the physiological temperature, thus aiding in the choice of the optimum in situ gel formulation.…”

The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel

“…The cumulative release percentages of MMC in the TA/MMC-PPH hydrogel were fitted to the zero-order release model, the first-order release model, the Higuchi model, and the Ritger-Peppas model ( Table 4 ). The appropriate model can be judged based on the magnitude of R 2 , which is more significant, indicating a better fit to the release characteristics of the gel [ 18 ]. In terms of the release rate, the fit of the first-stage release model (R 2 = 09929) was better than that of the zero-order release model (R 2 = 0.7727).…”

“…Thermosensitive hydrogels have been widely investigated for their unique sol-gel phase-transition behavior and their excellent biocompatibility and biodegradability in the prevention of postoperative adhesion [ 13 , 17 ]. Poloxamer 407 (P407) is one of the most commonly used thermosensitive materials for preparing thermosensitive hydrogels [ 18 , 19 ]. It is a nonionic PEO-PPO-PEO triblock copolymer consisting of a central hydrophobic chain of polypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene oxide (PEO) [ 20 ].…”