Mixture Of Pluronic Research Articles

A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase-Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

Tri-block co-polymer nanocarriers for enhancement of oral delivery of felodipine: preparation, in vitro characterization and ex vivo permeation

This study aimed to prepare, optimize and characterize novel felodipine-loaded polymeric nanomicelles, using a pluronic mixture of F127 and P123. Thin-film hydration method was adopted for the preparation of different polymeric nanomicelles (T1–T12) according to a 41.31 full factorial design. Factors studied were: Pluronic®:drug ratio (P:D ratio) (10, 20, 30 and 40 w/w) and percent of hydrophilic polymer (F127%) (33.33%, 50% and 66.67% w/w). Optimization criteria were to maximize transmittance percent (T%) and entrapment efficiency percent (EE%) and to minimize particle size (PS) and polydispersity index (PDI). The optimized formulation was further characterized by DSC, FTIR and 1H NMR studies. It was also subjected to stability testing and ex vivo permeation using rabbit intestines. Spherical nanomicelles of particle size ranging from 26.18 to 87.54 nm were successfully obtained. The optimized formulation was found to be the already prepared formulation T12 (P:D ratio of 40 and 66.67% F127) with suitable T% and EE% of 95.12% and 91.75%, respectively. DSC, FTIR and 1H NMR studies revealed felodipine (FLD) incorporation within T12 nanomicelles. T12 enhanced the ex vivo intestinal permeation of FLD when compared to a drug suspension and showed good stability. Therefore, pluronic nanomicelles could be promising for improved oral delivery of FLD.

Co-micellized Pluronic mixture with thermo-sensitivity and residence stability as an injectable tissue adhesion barrier hydrogel.

Although the tissue adhesion which leads to various complications frequently occurs after surgery, the development of an ideal tissue adhesion barrier is still a challenge. In this study, a thermo-sensitive hydrogel, which can fulfill the essential requirements of tissue adhesion barrier (that is, ease of handling for surgeon, flowing down prevention after application, stable residence on the injury during wound healing, and no use of toxic additives), was developed using biocompatible polyethylene glycol-polypropylene glycol copolymers (Pluronic F127/F68/P123 mixture). From the in vitro cell culture and in vivo animal study, it was observed that the Pluronic mixtures showed sol-gel transition at approximately body temperature (for easy injection or coating on the injury site and flowing down prevention after application) and prolonged residence stability in aqueous environment (> ∼7 days for stable protection of injury tissues/organs during wound healing), and thus was highly effective for the prevention of tissue adhesion without adverse tissue responses. Based on these results, the Pluronic F127/F68/P123 mixture itself (without any additives) can be a good candidate as an injectable or coatable tissue adhesion barrier hydrogel applicable to various injury tissues in terms of ease of use, effectiveness, and safety. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 172-182, 2018.

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

Influence of surface properties of polymeric nanoparticles on their membrane affinity

Biodegradable polylactic/glycolic acid copolymers are widely used as colloidal drug delivery systems. PLGA nanoparticles were prepared using non-ionic, PEO-containing block copolymer (Pluronic) and charged polymeric (PEI) surface modifiers. Physicochemical properties such as size, size distribution, zeta potential, surface composition, and colloid stability were compared to their behavior at interfaces. Adhesion of the PLGA nanoparticles to solid surface, accumulation at water surface and their cell membrane affinity (using a Langmuir lipid monolayer as a model system) were characterized. Significant differences were observed in surface activity and adhesion as well as in membrane affinity of nanoparticles depending on their surface composition. The interplay of electrostatic and steric effects resulted in sufficient colloid stability and maximum membrane affinity for the system stabilized with the mixture of Pluronic and PEI.

Characterization of a Reversible Thermoresponsive Gel and Its Application to Oligonucleotide Separation

Pluronic mixtures of F87 (E61P40E61) and F127 (E99P69E99), with E and P being poly(ethylene oxide) and poly(propylene oxide), respectively, have been used as effective separation media for the separation of small charged biomacromolecules, such as oligonulceotide fragments, by microchip electrophoresis. The temperature-dependent solubility of the middle block (P40 or P69) enables a convenient micelle formation of the triblock copolymer by self-assembly, forming ordered gel-like macrolattice structures at high polymer concentrations or high temperatures. Laser light scattering (LLS) and small-angle X-ray scattering (SAXS) were used to investigate the solution behavior, including the gel structure. Micelles of the F87/F127 mixture solution at different weight ratios almost had a constant hydrodynamic radius of about 10.6 nm, except for the pure F87 solution with a hydrodynamic radius size of about 6.3 nm. The aggregation number of the micelle increased from ∼5 to ∼17 with an increase in the F127 content in ...

Photo-cross-linkable and thermo-responsive hydrogels containing chitosan and Pluronic for sustained release of human growth hormone (hGH)

A Pluronic/chitosan hydrogel was prepared by employing di-acrylated Pluronic and acrylated chitosan for thermo-responsive and photo-cross-linkable in situ gelation. Mixtures of diacrylated Pluronic and acrylated chitosan were transformed to physical gels at elevated temperatures and the gelation temperature of the hydrogels gradually increased by increasing chitosan content in the hydrogels from 0% to 15%. Photo-cross-linked Pluronic/chitosan hydrogels were prepared by UV irradiation of the physical gels above their gelation temperatures. Hydrogels with a long photo-cross-linking time showed low degradation rates and chitosan contents in the hydrogels also impeded the degradation rates of the hydrogels, which was caused by a high degree of inter-connected polymer networks between acrylated Pluronic and acrylated chitosan. Human growth hormone (hGH), mixed with the mixture of Pluronic and chitosan, was photo-cross-linked to prepare biodegradable hGH hydrogels. The hydrogels containing hGH showed sustained release profiles for those with long photo-cross-linking times and high chitosan contents in the hydrogel. The hydrogels with a long cross-linking time showed impeded release of the protein and high content of chitosan in the hydrogels also decreased burst release of hGH from the hydrogels while hGH was rapidly released out for the hydrogels with low content of chitosan.

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

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.