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Thermally-induced gelling systems based on Poloxamer 407 (PL) and polysaccharides are known for their biomedical applications; however, phase separation frequently occurs in mixtures of poloxamer and neutral polysaccharides. In the present paper, the carboxymethyl pullulan (CMP) (here synthesized) was proposed for compatibilization with poloxamer (...
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... the number in subscript represents the sub degree with carboxymethyl groups. The characterization of pullulan deriva conductometric titration and FT-IR spectroscopy ( Figure S1) is presented Supplementary Materials. The general structures of CMP and PL are presented i 1. ...
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... equation fits the experimental intensity correlation functions for poloxamer solution at temperatures T ≥ 21 • C (Figure 9b). The decay times obtained by fitting the experimental data with the Equations (4) and (5) are presented in Figure 10a. The fast relaxation process is almost independent of the temperature, but the amplitude of this mode is higher at low temperatures where the unimers are predominant. ...
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... a further increase in the temperature, the time at which the power-low tail begins (τ*) moves to longer times and the amplitude of the power-low tail (A 3 ) rises from 0.1 at 21 • C to around 0.25, showing that the increasing physical interactions between the micelles restricts the movement of the system. In order to study the behavior of both polymers (the block copolymer and polyelectrolyte), DLS experiments with increasing temperature were also performed for a 1% aqueous solution of CMP0.95 (Figure 10b-inset). Two relaxation modes were observed for CMP0.95, as expected for a polyelectrolyte in salt-free solution [78]. ...
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... relaxation modes were observed for CMP0.95, as expected for a polyelectrolyte in salt-free solution [78]. The fast mode can be interpreted in this case as "mutual diffusion" (coupled diffusion of individual In order to study the behavior of both polymers (the block copolymer and polyelectrolyte), DLS experiments with increasing temperature were also performed for a 1% aqueous solution of CMP 0.95 (Figure 10b-inset). Two relaxation modes were observed for CMP 0.95 , as expected for a polyelectrolyte in salt-free solution [78]. ...
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... FIC curves kept the same shape with the increase in the temperature. The decay times obtained by fitting the curves with Equation (4) are presented in Figure 10b. The decay times of the fast mode (5 × 10 −6 -2 × 10 −6 ) and of the slow mode (5 × 10 −2 -3 × 10 −2 ) are practically temperature independent. ...
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... from these considerations, the dynamical behavior of poloxamer in the presence of different concentrations of CMP 0.95 was then analyzed. Figure 11a-c present the intensity correlation functions g (2) (q, t) − 1 at different temperatures for PL17/CMP 0.95 -0.4, PL17/CMP 0.95 -1 and PL17/CMP 0.95 -3. ...
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... behavior as a function of time during cycles of low-high-low deformations is usually investigated for such materials. In the present study, the thixotropic behavior was analyzed for the PL-based samples and the results are given in Figure 12. Low strains of 1% were alternated every 300 s with increasing high deformations for 5 cycles: 1-50%; 2-100%; 3-200%; 4-500%; and 5-1000%. ...
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... modulus before the first cycle elastic modulus after cycle n × 100 (7) of time during cycles of low-high-low deformations is usually investigated for such materials. In the present study, the thixotropic behavior was analyzed for the PL-based samples and the results are given in Figure 12. Low strains of 1% were alternated every 300 s with increasing high deformations for 5 cycles: 1-50%; 2-100%; 3-200%; 4-500%; and 5-1000%. ...
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... all samples, there is a high degree of recovery showing the ability of the micellar structure to be rapidly reestablished once the external stress is removed. However, particular behaviors can be depicted by calculating the degree of structure recovery after each strain cycle as: 100 cycle after modulus elastic cycle first the before modulus elastic (%) × = n R (7) According to Figure 13, for samples PL17/CMP0.95-0.4 and PL17/CMP0.95-1, the network structure is strengthened after removing the applied strains, suggesting an increase in intermolecular interactions and structure reorganization, possibly due to changes in conformation under the action of mechanical forces. ...
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... PL17/CMP0.95-3 is not able to recover its structure after high deformations, with the R value decreasing from 99% after cycle 1 to about 60% after cycle 4 and 5. According to Figure 13, for samples PL17/CMP 0.95 -0.4 and PL17/CMP 0.95 -1, the network structure is strengthened after removing the applied strains, suggesting an increase in intermolecular interactions and structure reorganization, possibly due to changes in conformation under the action of mechanical forces. By increasing the applied strain, these interactions are disturbed and R value decreases from 143% after cycle 1 to 99% after cycle 5. ...
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... 2023, 15, x FOR PEER REVIEW 17 of Figure 13. The degree of structural recovery after applying step strains cycles. ...
Citations
... Poloxamer 407 gels at body temperature. Hydrogen connections make F-127 more soluble in low-temperature water than in high-temperature water (Popescu et al. 2023). ...
Background
Ophthalmic in situ gel is a novel preparation. It can be instilled into the eye as a liquid but gels upon contact with the ocular surface, generating a sustained-release depot of the drug.
The main body of the abstract
Among drug delivery modalities, ocular drug administration requires careful study and parameter assessment. This is because the eyes are sensitive and require careful care. Conventional ocular administration techniques quickly eliminate formulated compounds, minimizing epithelial interaction. This review covers polymers used in ocular medication delivery, their uses, and their drawbacks. The in situ gelling mechanism converts liquid formulations into gels under certain physiological or environmental conditions. When they contact the ocular surface, in situ ocular gels undergo this transformation for medication administration. Different mechanisms drive this change, depending on the gel's formulation and desired properties. Temperature-, pH-, and ion-induced gelation are common processes of in situ ocular gel formation. The medicine's physicochemical qualities, desired drug release kinetics, ocular environment, and patient comfort determine the mechanism. Researchers can create ocular gels that transport medications, improve bioavailability, and increase patient compliance by carefully formulating and understanding the in situ gelation mechanism. These polymers are useful in prodrug research and ocular penetration enhancement. The article thoroughly discusses polymeric systems and creates a viable ophthalmic drug delivery formulation.
Short conclusion
In conclusion, in situ ocular gels advance ocular medication delivery. These gels overcome various difficulties of current delivery strategies for ocular therapeutics and provide a diverse and effective platform. In situ gelling, where the liquid formulation becomes a gel when it contacts ocular tissues, improves medication retention, bioavailability, and contact time.
... Alg or κ-Carr addition was efficient for low values of strain 50% or 100%, but the structure was disturbed at high values of strain (1000%). Similar effect was recently reported for PL samples in presence of carboxymethyl pullulan for concentrations below 1% [67]. PL gels in the presence of 1% CS or XG in NaCl solution presented modest selfhealing ability, the structure was strongly perturbed by applying high strains that belonged to non-linear range of viscoelasticity, and the network strength decreased after each cycle of deformation. ...
Thermoresponsive Pluronic® F127 (PL) gels in water were investigated through rheological tests in different shear conditions. The gel strength was tuned with the addition of 1% polysaccharide solution. In the presence of xanthan gum (XG), the viscoelastic behavior of PL-based hydrogels was improved in aqueous environment, but the rheological behavior was less changed with the addition of XG in PBS solutions, whereas in the presence of 0.1 M NaCl, the viscoelastic parameters decreased. PL micellar networks exhibited a self-healing ability, recovering their initial structure after applying cycles of high strain. The rheological characteristics of the PL hydrogel changed with the addition of 1% polysaccharides (xanthan gum, alginate, κ-carrageenan, gellan, or chitosan). PL/polysaccharide systems form temperature-responsive hydrogels with shear thinning behavior, yield stress, and self-healing ability, being considered a versatile platform for injectable biomaterials or bioinks. Thus, in the presence of xanthan gum in aqueous medium, the gel strength was improved after applying a high strain (the values of elastic modulus increased). The other investigated natural polymers induced specific self-healing behaviors. Good performances were observed with the addition of gellan gum, alginate, and κ-carrageenan, but for high values of strain, the ability to recover the initial structure decreased. A modest self-healing behavior was observed in the presence of chitosan and xanthan gum dissolved in NaCl solution.
... The ultrasonic velocity, dynamic scattering, light scattering, small-angle X-ray diffraction, small-angle neutron scattering, rheology and electrolyte behavior of the P407 aqueous solution were studied [26][27][28][29]. It was found that the gelation process was the result of micellar properties (aggregation number and micellar symmetry, etc.) changes, micellar polymerization and interaction [30]. ...
Most injectable preparations for the articular cavity are solution-type preparations that are frequently administered because of rapid elimination. In this study, triptolide (TPL), an effective ingredient in the treatment of rheumatoid arthritis (RA), was prepared in the form of a nanoparticle thermosensitive gel (TPL-NS-Gel). The particle size distribution and gel structure were investigated by TEM, laser particle size analysis and laser capture microdissection. The effect of the nanoparticle carrier material PLGA on the phase transition temperature was investigated by 1H variable temperature NMR and DSC. The tissue distribution, pharmacokinetic behavior, four inflammatory factors and therapeutic effect were determined in a rat RA model. The results suggested that PLGA increased the gel phase transition temperature. The drug concentration of the TPL-NS-Gel group in joint tissues was higher than that in other tissues at different time points, and the retention time was longer than that of the TPL-NS group. After 24 days of administration, TPL-NS-Gel significantly improved the joint swelling and stiffness of the rat models, and the improvement degree was better than that of the TPL-NS group. TPL-NS-Gel significantly decreased the levels of hs-CRP, IL-1, IL-6 and TNF-α in serum and joint fluid. There was a significant difference between the TPL-NS-Gel and TPL-NS groups on Day 24 (p < 0.05). Pathological section results showed that inflammatory cell infiltration was lower in the TPL-NS-Gel group, and no other obvious histological changes were observed. Upon articular injection, the TPL-NS-Gel prolonged drug release, reduced the drug concentration outside the articular tissue and improved the therapeutic effect in a rat RA model. The TPL-NS-Gel can be used as a new type of sustained-release preparation for articular injection.
... PULL and its derivatives present improved properties and are suitable for drug delivery systems [263,267,276], wound dressings, or tissue engineering applications [277][278][279][280][281]. A glutathione and pH dual-responsive drug delivery system composed of CM and oxidized PULL hydrogel was used to encapsulate methotrexate (an anticancer drug) [282,283] loaded on mesoporous silica nanoparticles [282]. ...
Hydrogels are three-dimensional networks with a variety of structures and functions that have a remarkable ability to absorb huge amounts of water or biological fluids. They can incorporate active compounds and release them in a controlled manner. Hydrogels can also be designed to be sensitive to external stimuli: temperature, pH, ionic strength, electrical or magnetic stimuli, specific molecules, etc. Alternative methods for the development of various hydrogels have been outlined in the literature over time. Some hydrogels are toxic and therefore are avoided when obtaining biomaterials, pharmaceuticals, or therapeutic products. Nature is a permanent source of inspiration for new structures and new functionalities of more and more competitive materials. Natural compounds present a series of physico-chemical and biological characteristics suitable for biomaterials, such as biocompatibility, antimicrobial properties, biodegradability, and nontoxicity. Thus, they can generate microenvironments comparable to the intracellular or extracellular matrices in the human body. This paper discusses the main advantages of the presence of biomolecules (polysaccharides, proteins, and polypeptides) in hydrogels. Structural aspects induced by natural compounds and their specific properties are emphasized. The most suitable applications will be highlighted, including drug delivery, self-healing materials for regenerative medicine, cell culture, wound dressings, 3D bioprinting, foods, etc.
