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This study investigates the reinforcement of pluronic (PF127) based temperature responsive hydrogels with photosensitive functionalities to create smart and injectable materials. For this purpose, 4‐[4‐[(4‐phenyl)azo]phenoxy] methacrylate (PAzPMA) was synthesized and further polymerized via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The structures of the copolymers were characterized by several techniques such as Fourier‐transform infrared (FT‐IR), nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The azobenzene‐functionalized copolymer was combined with P127 solid polymer in micelle form and with P127 micelles in solid form to obtain PF127‐AzoMx and PF127‐AzoPx gels, respectively. When the temperature profiles of the PF127‐AzoMx and PF127‐AzoPx systems were compared with PF127, sol–gel phase transition were shifted to lower temperatures due to stronger hydrophobic interactions. Additionally, different concentrations of N,N,N‐trimethyl chitosan (f‐chitosan) were added to the gel systems and their rheological properties were investigated by exposing them to UV light. It has been observed that the presence and concentration of f‐chitosan are important for the variation of the interactions' strength between the micelles. The study highlights the potential of multifunctional hydrogels for specific biomedical applications that combine sensitivity to both thermal and optical stimuli for controlled drug delivery and tissue engineering purposes. [ABSTRACT FROM AUTHOR]

Essential oils are a vast class of compounds that have many interesting therapeutical properties. In this sense, tea tree oil (TTO) stands out for its antioxidant, antifungal, antibacterial, anti-inflammatory, and antihyperproliferative potential. However, the low stability and solubility of these compounds can limit their therapeutical capacity, making it necessary to adopt a strategy to overcome this mishap. In that regard, nanoencapsulation can be highlighted as a promising maneuver capable of protecting the active and increasing its solubility in water, promoting greater compatibility and bioavailability. Based on the above, the main objective of this study was to evaluate polycaprolactone/Pluronic F-127 PCL/F-127 polymeric nanoparticles loaded with 10–30% w/w TTO obtained via nanoprecipitation. The obtained particles were evaluated by atomic force microscopy and UV–Vis spectroscopy to determine retention efficiency and obtain the release profile (with the evaluation of release models), time-domain nuclear magnetic resonance, antimicrobial activity, and cytotoxicity in fibroblasts and epithelial cells. The obtained results show the formation of particles of spherical-type morphology particles with smooth surfaces and particle sizes around 400 nm, with retention efficiencies between 60 and 70% and sustained release profile for up to about 6 or 7 h and compatible with the Higuchi model. Regarding the antimicrobial activity of the systems, it was observed that TTO presents antimicrobial activity against the evaluated strains (S. aureus, C.albicans, and E.coli) and that the encapsulation process can increase the activity against the strain of E. coli. Finally, the cytocompatibility analyses showed that the NNPs obtained are not cytotoxic to the cell lines evaluated. [ABSTRACT FROM AUTHOR]

Hypertension, also known as high blood pressure, is a serious medical condition that affects billions of people worldwide. Nebivolol hydrochloride, a β1–adrenergic blocking agent, is used by the oral route in the treatment of hypertension and congestive heart failure. However, its lipophilic nature and poor aqueous solubility restricts its oral bioavailability. To overcome limitations related with conventional oral formulations of the drug, uncoated and polymer–coated liposomes were developed and evaluated. Liposomes loaded with nebivolol hydrochloride were prepared by thin–film hydration method and characterized. The influence of chitosan or pluronic (F127) coating on the liposome properties was evaluated in terms of physicochemical characteristics, stability in simulated gastrointestinal fluids, mucin interaction, in vitro drug release and cytotoxicity studies. It was observed that coating the liposomes with either chitosan or pluronic affected the size, surface charge and encapsulation efficiency of the formulations. The surface morphology studies confirmed the vesicular shape of liposomes. The results obtained indicated that both polymer–coated liposome formulations maintained their stability in simulated gastrointestinal fluids and showed significant in vitro interaction with mucin. Polymer–coated liposome formulations showed much better cumulative release of the drug than uncoated liposomes. No aggregation was observed at the end of four–week storage period and low toxicity in Caco–2 cells was measured. The results demonstrated that polymer coating of liposomes could enhance the in vitro release of nebivolol hydrochloride and interaction with mucin following oral administration and might be attractive alternative nanocarriers to traditional oral formulations. [ABSTRACT FROM AUTHOR]

This study investigates the relationship between the molecular structure and foaming of poly(ethylene glycol) and poly(propylene glycol) triblock copolymers in Portland cement pastes. Four copolymers with different molecular structures were studied at varying concentrations. All copolymers showed a reduction in surface tension of the cement pore solution; however, only some of them demonstrated foaming and air entraining in cement paste. The results indicated that the molecular structure parameter, hydrophilic-to-lipophilic balance (HLB), has a direct relationship with the foaming and air-entraining performance of the copolymers. The total organic carbon measurements showed very small adsorption of these non-ionic copolymers on hydrating cement particles due to the lack of surface charge needed to interact with the heterogeneously charged surface of hydrating cement. In addition, these copolymers did not seem to affect the flow of cement paste due to a lack of adsorption on cement particles. The cement paste modified with the copolymers showed increased water sorption compared to the control paste due to the increased capillary porosity and slight increase in pore surface hydrophilicity. However, the freeze-thaw resistance was shown to improve with an increase in the number of air voids in the modified cement pastes. The findings establish the relationship between molecular properties of copolymers and their air-entraining performance in cement paste to mitigate the damages caused by freeze-thaw action. [ABSTRACT FROM AUTHOR]

The effect of pluronics L61 and F68 containing hydrophobic poly(propylene oxide) blocks of the same length and hydrophilic poly(ethylene oxide) blocks of different lengths on the conductance of planar bilayer lipid membranes made of azolectine is investigated. The conductance of these membranes increases as the concentration of both pluronics increases. For the same concentration of pluronics in solution, the conductance is higher for L61. Based on the literature data, the concentration of pluronics bound with the bilayer is calculated. For the close concentration of membrane-bound pluronics, the conductance of membranes is also close. It is concluded that in the first approximation, the appearance of the same hydrophobic parts of pluronics L61 and F68 in a membrane is accompanied by the same increase in its conductance. The conductance vs. concentration curves are superlinear for L61 and sublinear for F68. In the presence of either of these pluronics, the conduction spikes with the amplitude from 10 to 300 pSm and higher are observed for approximately 40% of membranes. These surges of conductance are associated with the appearance of conductive pores or defects in the membrane. The number of pores observed in the membrane is a random variable with a large scatter and does not correlate with the pluronic concentration. The difference between the average pore conductivities for membranes containing L61 and F68 is statistically insignificant. [ABSTRACT FROM AUTHOR]

The effect of the diphenylalanine (Phe-Phe) amino acid on the rate of tryptophan photooxidation catalyzed by photosensitizers (PS) of different natures: dimegin (DMG), fluorinated tetraphenylporphyrin (FTPP), photoditazine (PD) and methylene blue (MB) was studied. It was shown that in the presence of Phe-Phe, the effective constant of photooxidation of the substrate catalyzed by DMG, PD and MB in the aqueous phase decreases. However, the introduction of the amphiphilic polymer Pluronic F127 into the systems allows not only to restore, but also to increase the activity of the PS in the processes of photosensitized oxidation. In particular, the activity of dimegin solubilized by Pluronic F127 in the presence of Phe-Phe is higher than the activity of both pure porphyrin and solubilized DMG. In addition, the activity of the hydrophobic FTPP solubilized by Pluronic also increases. At the same time, a study of the luminescence of singlet oxygen generated by solubilized FTPP in the absence and presence of Phe-Phe revealed that the dipeptide does not influence the processes of 1О2 generation. It was suggested that micellar catalysis influences the activity of solubilized PS in the presence of a biologically active dipeptide. [ABSTRACT FROM AUTHOR]

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications. [ABSTRACT FROM AUTHOR]

Pluronic F127 dimethacrylate (F127-DM) inks exhibit potential for 3D printing biomaterials due to their combined gelation and photo-crosslinking capabilities. Previous studies have explored their application in extrusion 3D printing of medical devices, relying on their long-range micellar ordering to impart mechanical stability, stretchability, and control over drug delivery. However, there is a lack of information regarding the impact of the extrusion and photo-crosslinking processes on the micellar ordering of F127-DM. Herein, we employed in operando 3D printing synchrotron small-angle X-ray scattering (SAXS) to analyze the influence of various printing parameters, including nozzle shape, nozzle size, extrusion rate, ink composition, and photo-crosslinking, on the micellar ordering of F127-DM. Our findings from 2D SAXS patterns indicate orientation of the micellar packing clusters along the flow direction. The nozzle diameter and shape emerged as crucial parameters, leading to increased disruption of long-range ordering. Furthermore, 1D SAXS curves during UV-Vis light exposure and photo-crosslinking revealed a partial preservation of the micellar packing structure, with cluster size reduction, and coexisting with randomly distributed micelles and unimers. These results underscore the importance of in operando synchrotron experiments for the systematic study of 3D printing parameters from a nanostructure perspective. [ABSTRACT FROM AUTHOR]

Plant probiotic bacteria are being increasingly used to maximize both the productivity and quality of field crops. Pseudomonas chlororaphis O6 (PcO6) is a plant root colonizer with probiotic activities. This bacterium produces an array of metabolites, including a group of phenazines that are functional in plant protection. The paper reports responses of PcO6 to a nonionic triblock copolymer surfactant, Pluronic F68. This Pluronic exhibits membrane "healing" activity and improves cryopreservation recovery in eukaryotic cells. The product is FDA-approved and is applied as an adjuvant in formulations used in agriculture, medicine, and biotechnology. Growth of PcO6 on lysogeny broth at 25 °C was unhindered by 0.1 and 1.0 g/L F68, reduced at 10 g/L, and with significant inhibition at 100 g/L F68; micelle formation could account for inhibited growth at higher doses. Phenazine production was not changed by F68, whereas the surfactant activity of F68 induced the spread of bacterial colonization on 0.5% agar. Exposure of cells to fluorescein-labeled F68 resulted in intense fluorescence, stable to washing, showing a direct association of the Pluronic with the bacterium. However, neither protection nor harm was found for PcO6 cells suspended in either 0.1% or 1% F68 after three freeze (−20 °C)/thaw cycles. These findings suggest that F68 could be compatible for use in agricultural formulations with little effect on probiotics such as PcO6. [ABSTRACT FROM AUTHOR]

Aiming at the fundamental understanding of solvent effects in amphiphilic polymer systems, we considered poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO-PPO-PEO) block copolymers in water mixed with an ionic liquid—ethylammonium nitrate (EAN), 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), or 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4)—and we investigated the hexagonal lyotropic liquid crystal structures by means of small-angle X-ray scattering (SAXS). At 50% polymer, the hexagonal structure (cylinders of self-assembled block copolymer) was maintained across the solvent mixing ratio. The effects of the ionic liquids were reflected in the characteristic length scales of the hexagonal structure and were interpreted in terms of the location of the ionic liquid in the self-assembled block copolymer domains. The protic ionic liquid EAN was evenly distributed within the aqueous domains and showed no affinity for the interface, whereas BMIMPF6 preferred to swell PEO and was located at the interface so as to reduce contact with water. BMIMBF4 was also interfacially active, but to a lesser extent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plant probiotic bacteria are being increasingly used to maximize both the productivity and quality of field crops. Pseudomonas chlororaphis O6 (PcO6) is a plant root colonizer with probiotic activities. This bacterium produces an array of metabolites, including a group of phenazines that are functional in plant protection. The paper reports responses of PcO6 to a nonionic triblock copolymer surfactant, Pluronic F68. This Pluronic exhibits membrane “healing” activity and improves cryopreservation recovery in eukaryotic cells. The product is FDA-approved and is applied as an adjuvant in formulations used in agriculture, medicine, and biotechnology. Growth of PcO6 on lysogeny broth at 25 °C was unhindered by 0.1 and 1.0 g/L F68, reduced at 10 g/L, and with significant inhibition at 100 g/L F68; micelle formation could account for inhibited growth at higher doses. Phenazine production was not changed by F68, whereas the surfactant activity of F68 induced the spread of bacterial colonization on 0.5% agar. Exposure of cells to fluorescein-labeled F68 resulted in intense fluorescence, stable to washing, showing a direct association of the Pluronic with the bacterium. However, neither protection nor harm was found for PcO6 cells suspended in either 0.1% or 1% F68 after three freeze (−20 °C)/thaw cycles. These findings suggest that F68 could be compatible for use in agricultural formulations with little effect on probiotics such as PcO6.

Tarek A Ahmed,1 Ehab MM Ali,2 Abdelsattar M Omar,3 Alshaimaa M Almehmady,1 Khalid M El‐Say1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia; 2Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi ArabiaCorrespondence: Tarek A Ahmed, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia, Tel +966 2 640 0000 Ext 22250, Email tabdelnapy@kau.edu.saBackground: Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations.Materials and Methods: Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed.Results: The prepared formulations were in the nano-size range (34.01 ± 2.00– 278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC50 against MCF-7 (4.51 μg/mL) and T47D (8.22 μg/mL) cancer cells. When T47D cells were treated with IC50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death.Conclusion: These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer.Keywords: ezetimibe, TPGS, pluronic, micelles, anticancer activity, MCF7, T47D

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant (< 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior. [ABSTRACT FROM AUTHOR]

Cancer is a disease that continues to greatly impact our society. Developing new and more personalized treatment options is crucial to decreasing the cancer burden. In this study, we combined magnetic polysaccharide microparticles with a Pluronic thermoresponsive hydrogel to develop a multifunctional, injectable drug delivery system (DDS) for magnetic hyperthermia applications. Gellan gum and alginate microparticles were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) with and without coating. The magnetic microparticles' registered temperature increases up to 4 °C upon the application of an alternating magnetic field. These magnetic microparticles were mixed with drug-loaded microparticles, and, subsequently, this mixture was embedded within a Pluronic thermoresponsive hydrogel that is capable of being in the gel state at 37 °C. The proposed DDS was capable of slowly releasing methylene blue, used as a model drug, for up to 9 days. The developed hydrogel/microparticle system had a smaller rate of drug release compared with microparticles alone. This system proved to be a potential thermoresponsive DDS suitable for magnetic hyperthermia applications, thus enabling a synergistic treatment for cancer. [ABSTRACT FROM AUTHOR]

Pluronic F127 dimethacrylate (F127-DM) inks exhibit potential for 3D printing biomaterials due to their combined gelation and photo-crosslinking capabilities. Previous studies have explored their application in extrusion 3D printing of medical devices, relying on their long-range micellar ordering to impart mechanical stability, stretchability, and control over drug delivery. However, there is a lack of information regarding the impact of the extrusion and photo-crosslinking processes on the micellar ordering of F127-DM. Herein, we employed in operando 3D printing synchrotron small-angle X-ray scattering (SAXS) to analyze the influence of various printing parameters, including nozzle shape, nozzle size, extrusion rate, ink composition, and photo-crosslinking, on the micellar ordering of F127-DM. Our findings from 2D SAXS patterns indicate orientation of the micellar packing clusters along the flow direction. The nozzle diameter and shape emerged as crucial parameters, leading to increased disruption of long-range ordering. Furthermore, 1D SAXS curves during UV-Vis light exposure and photo-crosslinking revealed a partial preservation of the micellar packing structure, with cluster size reduction, and coexisting with randomly distributed micelles and unimers. These results underscore the importance of in operando synchrotron experiments for the systematic study of 3D printing parameters from a nanostructure perspective.

This study investigates the relationship between the molecular structure and foaming of poly(ethylene glycol) and poly(propylene glycol) triblock copolymers in Portland cement pastes. Four copolymers with different molecular structures were studied at varying concentrations. All copolymers showed a reduction in surface tension of the cement pore solution; however, only some of them demonstrated foaming and air entraining in cement paste. The results indicated that the molecular structure parameter, hydrophilic-to-lipophilic balance (HLB), has a direct relationship with the foaming and air-entraining performance of the copolymers. The total organic carbon measurements showed very small adsorption of these non-ionic copolymers on hydrating cement particles due to the lack of surface charge needed to interact with the heterogeneously charged surface of hydrating cement. In addition, these copolymers did not seem to affect the flow of cement paste due to a lack of adsorption on cement particles. The cement paste modified with the copolymers showed increased water sorption compared to the control paste due to the increased capillary porosity and slight increase in pore surface hydrophilicity. However, the freeze-thaw resistance was shown to improve with an increase in the number of air voids in the modified cement pastes. The findings establish the relationship between molecular properties of copolymers and their air-entraining performance in cement paste to mitigate the damages caused by freeze-thaw action.

Nanocomposite solid polymer electrolytes (NSPEs) with PVDF‐HFP/Pluronic as blend polymer matrix, graphene oxide (GO) as nanofiller, and LiClO4 are reported. FTIR spectroscopy reveals the crystal phase transformation of PVDF‐HFP from nonpolar α phase to electroactive γ phase upon salt addition that suggests the ion‐dipole interaction between the salt and the matrix. Further, Pluronic not only hinders the PVDF crystallization that increases the amorphous character of the matrix but also interacts with the salt and hence assists in salt dissociation in the blend matrix. The dc conductivity of PVDF‐HFP/Pluronic/LiClO4 blend SPE improves with increasing the Pluronic content reaching 0.73 × 10−6 Scm−1 at room temperature with 60 wt.% Pluronic. The dispersion of GO in the same blend SPE leads to a significant jump in room temperature ion conductivity (≈1.2 × 10−6 Scm−1) with 0.4% GO. Temperature‐dependent ion conductivity of the NSPEs reveals an Arrhenius type thermally activated process. The dc polarization data indicates that the conductivity is predominantly due to ions. Impedance plots exhibit a distorted semicircle at higher frequency and a tilted spike at lower frequency. The spike is an indication of ion diffusion and electrode polarization effect. Further, GO also has enhanced the mechanical properties of the fabricated NSPEs. [ABSTRACT FROM AUTHOR]

Chemical modification of the enzymes with biospecific macromolecules is used in various fields of biotechnology to impart new functions or improve their properties and is a fast and convenient way to get the final products. The preparation of highly active, stable, and functionally active conjugates of the thermostable luciferase through the NH2-groups or free SH-groups of the enzyme with target molecules of different molecular weight (albumin, avidin from chicken eggs, antibodies, and progesterone) is described. The obtained conjugates were successfully tested as a reporter in bioluminescent immunoassay for the detection of the molecules and pathogens. Thus, the luc-albumin (Luc-Alb) and luc-insulin (Luc-Ins) conjugates were used in competitive ELISA for the detection of an analyte (albumin or insulin) in the samples. Luc-progesterone (Luc-Pg) was used in the rapid homogeneous immunoassay of progesterone by the BRET technique with the detection limit of 0.5 ng/ml. Luciferase conjugates with avidin (Luc-Avi) and secondary and primary antibodies (Luc-RAM and Luc-Sal) were used for enzyme immunoassay detection of Salmonella paratyphi A cells with the cell detection limit of 5 × 104 CFU/ml. To reduce the detection limit of Salmonella cells, we developed a pseudo-homogeneous bioluminescent enzyme immunoassay of cells using a new matrix for the analyte capture—polystyrene microparticles coated with Pluronic F108, covalently labeled with Sal antibodies. This allowed to achieve efficient trapping of cells from solution, significantly reduced nonspecific sorption and decreased the cell detection limit to 2.7 × 103 CFU/ml without prior concentration of the sample. The methodology that was developed in this study can be applied for the development of novel bioanalytical systems based on firefly luciferases. [ABSTRACT FROM AUTHOR]

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development. [ABSTRACT FROM AUTHOR]

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

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.

The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved in vivo. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system. [ABSTRACT FROM AUTHOR]

Sprayable hydrogel formulations are promising topical treatments for skin wounds due to their ability to reduce application pain, prolong drug release, and provide moisture to promote skin healing. These viscoelastic materials, however, present challenges in spray ability which can be overcome using a thermoreversible hydrogels sprayed as lower viscosity liquids at cooler temperatures. The purpose of this research was to evaluate the impact of thermoreversible hydrogel formulation and device characteristics on topical spray patterns and to develop metrics to accurately describe surface coverage. Cold solutions of Pluronic F127 were prepared at 15, 17, and 20% (w/w) and tested to determine their rheological properties. Formulations were sprayed from hand-held atomizing pump dispersers under cold conditions and two distinct areas of their spray patterns analyzed: the concentrated core and the full spray pattern. Traditional analysis of spray patterns was conducted to determine major and minor axes, ovality, and total area. In addition, new scripts were developed to evaluate the concentrated core. The full spray pattern analysis quantified the total area over which the spray would extend a flat surface, while the concentrated core analysis quantified the continuous region where a drug dose would be concentrated. The combination of formulation viscosity, sprayer nozzle, and spray distance produced spray patterns from highly concentrated to highly dispersed. These parameters can be controlled to generate desired hydrogel spray patterns for application on skin surfaces. The developed metrics provide a basis for topical spray analysis that can inform future product performance. [ABSTRACT FROM AUTHOR]

Introduction: During cochlear implantation, electrode insertion can cause cochlear damage, inflammation, and apoptosis, which can affect the residual hearing. Nanoparticles are increasingly studied as a way to increase the availability of inner ear protective factors. We studied the effect on rats of Pluronic-coated gold nanoparticles (Plu-AuNPs) containing dexamethasone, which were applied locally in the rat’s middle ear following the implant procedure. Methods: Seven rats were used in the study. The right ear served as a model for the Dex-Plu-AuNP group. Following the intracochlear dummy electrode insertion through the round window, Dex-Plu-AuNPs were placed in the round window niche. In the right ear, following the same insertion procedure, free dexamethasone (Dex) was placed in the same manner. Auditory brainstem response thresholds (click stimulus, pure tones at 8 kHz, 16 kHz, 24 kHz, and 32 kHz) were measured before and one week after the procedure. A two-tailed T-test was used for the variables. Statistical significance was set as p < 0.05. Results: In the Dex-Plu-AuNP group, the threshold shift was less than that in the free dexamethasone group, but no statistical significance was noted between the groups. When compared individually, only the 8 kHz frequency showed statistically significant, better results after one week, in favor of the Dex-Plu-AuNP group. The mean postoperative 8 kHz threshold in the Dex-Plu-AuNPs was significantly lower than that of the control group (p = 0.048, t-test). For the other frequencies, statistical analysis showed no significant differences between the mean threshold shifts of the two cohorts. Conclusions: The local application of Plu-AuNPs containing dexamethasone following cochlear implantation may better protect the residual hearing than dexamethasone alone, but a larger sample size is needed to reach a possible statistical significance. Dex-Plu-AuNPs do not seem to cause ototoxicity and may be used as a carrier for other agents. In a clinical setting, Dex-Plu-AuNPs may have the effect of protecting lower frequencies in patients with partial deafness who are candidates for electric acoustic stimulation (EAS). If we consider this tendency, Dex-Plu-AuNPs may also be beneficial for patients with Ménière’s disease.

In this study, functional Pluronic F127 precursors were designed and synthesized for the preparation of thermosensitive hydrogels. Using linear Pluronic thioacetate and Pluronic multi-acrylate precursors, F127-based hydrogels were prepared through thioacetate deprotection-mediated Michael-type addition. The properties of these gels were compared to those obtained through free radical crosslinking of F127 diacrylate. Temperature was found to have a clear influence on gel swelling as a result of F127 thermoresponsiveness. The macromolecular architecture and functionality of the precursors were also optimized and characterized in terms of gelation kinetics and drug diffusion. In vitro tests were conducted on fibroblasts and endothelial cells to assess their response to cellular adhesion with Pluronic gels that were functionalized with an RGD peptide or pretreated with serum proteins to promote cell adhesion. This study provides a method for creating tailored hydrogels suitable for various biomedical applications, such as soft-tissue engineering, cell encapsulation, wound healing, and sustained delivery of therapeutic molecules. [ABSTRACT FROM AUTHOR]

Objectives: Rutin has been broadly applied for treating several diseases due to its pharmacological activities. However, its low aqueous solubility limits its absorption and bioavailability. This research aims to increase the solubility of rutin using cyclodextrin and to develop a temperature)triggered in situ gelling system for dermal application. Materials and Methods: The solubility of rutin was increased with sulfobutyl ether-β-cyclodextrin (SBE-β-CD). Rutin- SBE-β-CD inclusion complex was prepared by kneading and freeze dying method. Structural characterization was carried out using differential scanning calorimetry and fourier transform infrared spectroscopy. In situ gel formulations were prepared with pluronic F127 (PF127), a thermosensitive polymer, and chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer. In situ gel characteristics such as pH, clarity, gelation temperature, and viscosity were determined. Results: When the solubility diagrams were examined, it was concluded that SBE-β-CD showed a linear increase, therefore, AL-type diagram was selected. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. Three in situ gels were evaluated for their pH, gelling temperature, and the rheological behaviors, and one formulation was selected. It was observed that the formulations had a pH between 6-6.1, and their gelation temperature decreased with increasing PF127 that was between 20°C to 34°C. For the selected formulation (formulation E3), 0.5% rutin and rutin/SBE-β-CD were transferred to the in situ gelling system. Because of in vitro release studies, it was observed that the release of the rutin/SBE-β-CD inclusion complex containing NZ formulation showed a higher burst effect than the others and the release continued for 6 hours. Conclusion: The results indicated that the combination of PF127 and CH can be a hopeful in situ gelling vehicle for dermal delivery of rutin and rutin/SBE-β-CD. [ABSTRACT FROM AUTHOR]

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml−1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds [Display omitted] [ABSTRACT FROM AUTHOR]

Aiming at the fundamental understanding of solvent effects in amphiphilic polymer systems, we considered poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO-PPO-PEO) block copolymers in water mixed with an ionic liquid—ethylammonium nitrate (EAN), 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), or 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4)—and we investigated the hexagonal lyotropic liquid crystal structures by means of small-angle X-ray scattering (SAXS). At 50% polymer, the hexagonal structure (cylinders of self-assembled block copolymer) was maintained across the solvent mixing ratio. The effects of the ionic liquids were reflected in the characteristic length scales of the hexagonal structure and were interpreted in terms of the location of the ionic liquid in the self-assembled block copolymer domains. The protic ionic liquid EAN was evenly distributed within the aqueous domains and showed no affinity for the interface, whereas BMIMPF6 preferred to swell PEO and was located at the interface so as to reduce contact with water. BMIMBF4 was also interfacially active, but to a lesser extent.

Cancer is a disease that continues to greatly impact our society. Developing new and more personalized treatment options is crucial to decreasing the cancer burden. In this study, we combined magnetic polysaccharide microparticles with a Pluronic thermoresponsive hydrogel to develop a multifunctional, injectable drug delivery system (DDS) for magnetic hyperthermia applications. Gellan gum and alginate microparticles were loaded with superparamagnetic iron oxide nanoparticles (SPIONs) with and without coating. The magnetic microparticles’ registered temperature increases up to 4 °C upon the application of an alternating magnetic field. These magnetic microparticles were mixed with drug-loaded microparticles, and, subsequently, this mixture was embedded within a Pluronic thermoresponsive hydrogel that is capable of being in the gel state at 37 °C. The proposed DDS was capable of slowly releasing methylene blue, used as a model drug, for up to 9 days. The developed hydrogel/microparticle system had a smaller rate of drug release compared with microparticles alone. This system proved to be a potential thermoresponsive DDS suitable for magnetic hyperthermia applications, thus enabling a synergistic treatment for cancer.

The use of local intra-articular injection therapy for the treatment of osteoarthritis has experienced an increase in recent decades. With this treatment, frequent injections are necessary to obtain an adequate anti-inflammatory effect, which implies greater inconveniences for the patients. An alternative could be use injectable controlled release systems that allow to reduce the frequency of application. The aim of this research is to develop a system based on dexamethasone-loaded polycaprolactone particles dispersed in a thermosensitive chitosan/Pluronic® F-127 hydrogel. The microparticles were obtained by the double emulsion / solvent evaporation technique. The hydrogel is prepared from a physical mixture of chitosan and Pluronic® F127. The microparticle / hydrogel system was prepared by dispersing 50 mg of particles in 2 mL of the liquid hydrogel. The samples were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The cytocompatibility of the samples was evaluated using the C-28 cell line of human chondrocytes by the 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium (MTS) assay and a study of dexamethasone release in phosphate buffered saline solution (PBS) was carried out for 7 days. The particles have a defined spherical shape and a size between 4-14 µm. The characterization by Fourier transform infrared spectroscopy showed that there are no chemical interactions between chitosan and Pluronic® F127 in the hydrogel. All the analyzed samples were cytocompatible with the C-28 cell line. The release study showed that the system has greater control over dexamethasone release. The system proves to be a promising option as an intra-articular administration system in the pharmacological treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Breast cancer is a prevalent tumor and causes deadly metastatic complications. Myriad cancer types, including breast cancer, are effectively treated by methotrexate (MTX). However, MTX hydrophobicity, adverse effects and the development of resistance have inspired a search for new effective strategies to overcome these challenges. These may include the addition of a bioenhancer and/or encapsulation into appropriate nano-based carriers. In the present study, the anticancer effect of MTX was fortified through dual approaches. First, the concomitant use of piperine (PIP) as a bioenhancer with MTX, which was investigated in the MCF-7 cell line. The results depicted significantly lower IC50 values for the combination (PIP/MTX) than for MTX. Second, PIP and MTX were individually nanoformulated into F-127 pluronic nanomicelles (PIP-NMs) and F-127/P-105 mixed pluronic nanomicelles (MTX-MNMs), respectively, validated by several characterization techniques, and the re-investigated cytotoxicity of PIP-NMs and MTX-MNMs was fortified. Besides, the PIP-NMs/MTX-MNMs demonstrated further cytotoxicity enhancement. The PIP-NMs/MTX-MNMs combination was analyzed by flow cytometry to understand the cell death mechanism. Moreover, the in vivo assessment of PIP-NMs/MTX-MNMs was adopted through the Ehrlich ascites model, which revealed a significant reduction of the tumor weight. However, some results of the tumor markers showed that the addition of PIP-NMs to MTX-MNMs did not significantly enhance the antitumor effect. [ABSTRACT FROM AUTHOR]

Pluronics are a family of amphiphilic block copolymers broadly explored in the pharmaceutical field. Under certain conditions, Pluronics self-assemble in different structures including nanosized direct and reverse micelles. This review provides an overview about the main parameters affecting the micellization process of Pluronics, such as polymer length, fragments distribution within the chain, solvents, additives and loading of cargo. Furthermore, it offers a guide about the most common techniques used to characterize the structure and properties of the micelles. Finally, it presents up-to-date approaches to improve the stability and drug loading of Pluronic micelles. Special attention is paid to reverse Pluronics and reverse micelles, currently underexplored in the literature. Pluronic micelles present a bright future as drug delivery agents. A smart design and thorough characterization will improve the transfer to clinical applications. [ABSTRACT FROM AUTHOR]

Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol–gel transition temperatures within a suitable range (between 25 °C and 37 °C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile. [ABSTRACT FROM AUTHOR]

Prussian blue (PB) is a metal cluster nanoparticle (NP) of cyanide-bridged iron(II)–iron(III) and exhibits a characteristic blue color. Its peroxidase-, catalase-, and superoxide-dismutase-like activities effectively remove excess reactive oxygen species that induce inflammation and tumorigenesis. However, the dispersion of PB NPs is not sufficiently stable for their application in the biomedical field. In this study, we developed Pluronic-stabilized Prussian blue nanoparticles (PB/Plu NPs) using a series of Pluronic triblock copolymers as a template material for PB NPs. Considering the hydrophilic–lipophilic balance (HLB) values of the Pluronic series, including F68, F127, L35, P123, and L81, the diameters of the PB/Plu NPs decreased from 294 to 112 nm with decreasing HLB values. The smallest PB NP stabilized with Pluronic P123 (PB/PP123 NP) showed the strongest antioxidant and anti-inflammatory activities and wound-healing efficacy because of its large surface area. These results indicated that the spatial distribution of PB NPs in the micelles of Pluronic greatly improved the stability and reactive oxygen species scavenging activity of these NPs. Therefore, PB/Plu NPs using U.S.-FDA-approved Pluronic polymers show potential as biocompatible materials for various biomedical applications, including the treatment of inflammatory diseases in the clinic. [ABSTRACT FROM AUTHOR]

With the significant improvement of energy density and power density of electrochemical energy storage devices, a large amount of heat will be generated during operation, and fire or explosion may occur due to high internal temperature. However, the traditional method of controlling thermal runaway is slow and irreversible. Here, we investigate a reversible electrolyte system based on thermal-responsive polymers consisting of Pluronic F127, ionic liquid (IL) [EMIM]BF4, and a lithium salt. Pluronic-IL electrolyte responds by sol–gel transformation above the lower-critical solution temperature (LCST), which inhibits electrochemical energy conversion and effectively prevents thermal runaway at 160 ℃. We investigated the effects of operating temperature, lithium-ion concentration, and Pluronic concentration on electrochemical performance and proved that by regulating the concentration of Pluronic, the loss rate of capacitance can reach nearly 70%. It can be seen that this is a green and efficient method to control thermal runaway and may be practically used in lithium-ion batteries in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • Azithromycin was integrated in a thiolated pluronic nanoemulsion drug-delivery system. • The novel formulation was extremely potent in eradicating bacterial load. • Azithromycin solubility, mucoadhesion, stability and targeted drug delivery was attained. • The novel formulation shows great potential for peptic ulcer treatment. Peptic ulcer disease is a substantial health issue worldwide, owing to excessive use of non-steroidal anti-inflammatory drugs (NSAIDs) and poor hygienic conditions. Numerous therapeutic approaches including antibiotics and PPIs are commonly used, but these therapies are rendered with multi-drug resistance, increased frequency of dosing, less retention time, deceased safety, efficacy, and non-patient compliance. Herein, azithromycin (AZM), an expansive-spectrum antibiotic with notable anti-ulcer efficiency was integrated into a thiolated pluronic self- emulsifying drug delivery system (SEDDS) to enhance its solubility, mucoadhesion, stability, gastro-retention, and targeted drug delivery. Pluronics are triblock copolymers with excellent biocompatibility and amphiphilic properties, widely used in drug delivery, disease diagnosis, and treatment, among other applications. In vitro and in vivo tests were performed to assess the drug-release kinetics, H-pylori clearance, and efficacy. The optimized formulation possessed a size of 357 nm, PDI ≤ 0.5 and a zeta potential of 30 mV. Drug release was 85 % in 72 h, following Korsmeyer-Peppas model. Thiolated SEDDS proved to be extremely potent in eradicating bacterial load (40-load) when compared to alternative formulations. Furthermore, the retention duration, biofilm elimination and nanoparticle uptake were maximized. This novel thiolated SEDDS composition is highly recommended as it holds promising potential to markedly enhance the therapeutic outcomes of AZM in peptic ulcer treatment and overcomes the restrictions of current methodologies. The study not only boosts scientific comprehension of more effective drug-delivery techniques but also recommends significant implications for the broader disciplines of gastroenterology and personalized medicine. [ABSTRACT FROM AUTHOR]

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.

Introduction: During cochlear implantation, electrode insertion can cause cochlear damage, inflammation, and apoptosis, which can affect the residual hearing. Nanoparticles are increasingly studied as a way to increase the availability of inner ear protective factors. We studied the effect on rats of Pluronic-coated gold nanoparticles (Plu-AuNPs) containing dexamethasone, which were applied locally in the rat's middle ear following the implant procedure. Methods: Seven rats were used in the study. The right ear served as a model for the Dex-Plu-AuNP group. Following the intracochlear dummy electrode insertion through the round window, Dex-Plu-AuNPs were placed in the round window niche. In the right ear, following the same insertion procedure, free dexamethasone (Dex) was placed in the same manner. Auditory brainstem response thresholds (click stimulus, pure tones at 8 kHz, 16 kHz, 24 kHz, and 32 kHz) were measured before and one week after the procedure. A two-tailed T-test was used for the variables. Statistical significance was set as p < 0.05. Results: In the Dex-Plu-AuNP group, the threshold shift was less than that in the free dexamethasone group, but no statistical significance was noted between the groups. When compared individually, only the 8 kHz frequency showed statistically significant, better results after one week, in favor of the Dex-Plu-AuNP group. The mean postoperative 8 kHz threshold in the Dex-Plu-AuNPs was significantly lower than that of the control group (p = 0.048, t-test). For the other frequencies, statistical analysis showed no significant differences between the mean threshold shifts of the two cohorts. Conclusions: The local application of Plu-AuNPs containing dexamethasone following cochlear implantation may better protect the residual hearing than dexamethasone alone, but a larger sample size is needed to reach a possible statistical significance. Dex-Plu-AuNPs do not seem to cause ototoxicity and may be used as a carrier for other agents. In a clinical setting, Dex-Plu-AuNPs may have the effect of protecting lower frequencies in patients with partial deafness who are candidates for electric acoustic stimulation (EAS). If we consider this tendency, Dex-Plu-AuNPs may also be beneficial for patients with Ménière's disease. [ABSTRACT FROM AUTHOR]

[Display omitted] The disruption and overexpression of phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway in cancer results in tumor growth, metastasis, and survival. Treatment with common anthracyclines has confirmed cancer cells' dependence on PI3K pathway through overexpression of AKT. Moreover, combining HDAC inhibitor with anthracycline has shown the targeting of breast cancer stem cells. Therefore, it has been hypothesized that the co-delivery of PI3-Kδ/HDAC6 dual inhibitor with Epirubicin using polymeric nanoparticle could increase the anti-cancer treatment efficacy with reduced toxicity. Pluronic modified polylactic acid block copolymer (quatramer) was used for co-encapsulation of PI3-Kδ/HDAC6 and Epirubicin. The co-encapsulated nanoparticles, PI3-Kδ/HDAC6-Epi-NPs have shown size of 99 ± 3 nm, PDI of 0.18 ± 0.07 with a sustained and slow-release profile in non-physiological buffer (PBS, pH 7.4). The in-vitro cell proliferation inhibition studies done on 2D and 3D culture of breast cancer cell lines have confirmed the synergistic effect of PI3-Kδ/HDAC6-Epi-NPs with lower IC 50 values compared to PI3-Kδ/HDAC6-NPs and Epi-NPs. Additionally, intravenous twice a week treatment for three weeks with PI3-Kδ/HDAC6-Epi-NPs resulted in complete tumor eradication in the syngeneic breast tumor mice model. In comparison, the PI3-Kδ/HDAC6-NPs and Epi-NPs resulted in tumor growth inhibition of 15.86% and 81.59%, respectively. These studies predicted that clinical use of PI3-Kδ/HDAC6-Epi-NPs will be effective in breast cancer treatments. [ABSTRACT FROM AUTHOR]

Chlorin and bacteriochlorin derivatives are at present the most promising compounds used in photodynamic therapy. However, the use of these photosensitizers (PSs) in clinical practice is limited because of their low solubility in biological fluids. A water-soluble dipropoxybacteriopurpurinimide (DPBI) conjugate with Pluronic F-127 was synthesized in the present work. It was shown that conjugation with the poloxamer did not affect the physicochemical and photophysical properties of the starting PS. It was found during biological tests that the resulting conjugate had photodynamic and pharmacokinetic properties similar to those of the original DPBI pigment. The advantages of the proposed PS were demonstrated in an acute toxicity study. Intravenous administration of the PS at 10 times the therapeutic dose did not cause the death of test animals, in contrast to a DPBI emulsion in water. [ABSTRACT FROM AUTHOR]

Bacterial oral diseases are chronic, and, therefore, require appropriate treatment, which involves various forms of administration and dosing of the drug. However, multimicrobial resistance is an increasing issue, which affects the global health system. In the present study, a commercial amphiphilic copolymer, Pluronic F127, was used for the encapsulation of 1-(5′-nitrobenzimidazole-2′-yl-sulphonyl-acetyl)-4-aryl-thiosemicarbazide, which is an original active pharmaceutical ingredient (API) previously synthesized and characterized by our group, at different copolymer/API weight ratios. The obtained micellar systems, with sizes around 20 nm, were stable during 30 days of storage at 4 °C, without a major increase of the Z-average sizes. As expected, the drug encapsulation and loading efficiencies varied with the copolymer/API ratio, the highest values of 84.8 and 11.1%, respectively being determined for the F127/API = 10/1 ratio. Moreover, in vitro biological tests have demonstrated that the obtained polymeric micelles (PMs) are both hemocompatible and cytocompatible. Furthermore, enhanced inhibition zones of 36 and 20 mm were observed for the sample F127/API = 2/1 against S. aureus and E. coli, respectively. Based on these encouraging results, it can be admitted that these micellar systems can be an efficient alternative for the treatment of bacterial oral diseases, being suitable either by injection or by a topical administration. [ABSTRACT FROM AUTHOR]

The intra-articular administration of drugs has attracted great interest in recent decades for the treatment of osteoarthritis. The use of modified drugs has also attracted interest in recent years because their intra-articular administration has demonstrated encouraging results. The objective of this work was to prepare injectable-thermosensitive hydrogels for the intra-articular administration of Etanercept (ETA), an inhibitor of tumor necrosis factor-α. Hydrogels were prepared from the physical mixture of chitosan and Pluronic F127 with β-glycerolphosphate (BGP). Adding β-glycerolphosphate to the system reduced the gelation time and also modified the morphology of the resulting material. In vitro studies were carried out to determine the cytocompatibility of the prepared hydrogels for the human chondrocyte line C28/I2. The in vitro release study showed that the incorporation of BGP into the system markedly modified the release of ETA. In the in vivo studies, it was verified that the hydrogels remained inside the implantation site in the joint until the end of the study. Furthermore, ETA was highly concentrated in the blood of the study mice 48 h after the loaded material was injected. Histological investigation of osteoarthritic knees showed that the material promotes cartilage recovery in osteoarthritic mice. The results demonstrate the potential of ETA-loaded injectable hydrogels for the localized treatment of joints. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) has been studied for its biomedical applications due to its active biological properties. However, CUR has limitations such as poor solubility, low bioavailability, and rapid degradation. Thus, CUR was nanoformulated with the application of polymeric micelle. Previous studies of CUR-loaded Pluronic F127 nanoformulation (NanoCUR) were generally prioritized toward cancer cells and its therapeutic values. There are reports that emphasize the toxicity of CUR, but reports on the toxicity of NanoCUR on embryonic developmental stages is still scarce. The present study aims to investigate the toxicity effects of NanoCUR on the embryonic development of zebrafish (Danio rerio). NanoCUR was synthesized via thin film hydration method and then characterized using DLS, UV-Vis, FTIR, FESEM, and XRD. The toxicity assessment of NanoCUR was conducted using zebrafish embryos, in comparison to native CUR, as well as Pluronic F127 (PF) as the controls, and ROS assay was further carried out. It was revealed that NanoCUR showed an improved toxicity profile compared to native CUR. NanoCUR displayed a delayed toxicity response and showed a concentration- and time-dependent toxicity response. NanoCUR was also observed to generate a significantly low reactive oxygen species (ROS) compared to native CUR in ROS assay. Overall, the results obtained highlight the potential of NanoCUR to be developed in clinical settings due to its improved toxicity profile compared to CUR. [ABSTRACT FROM AUTHOR]

The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic–hydrophobic–hydrophilic and hydrophobic–hydrophilic–hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (ΔHmic) and entropy (ΔSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic–hydrophobic–hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties. [ABSTRACT FROM AUTHOR]

Chen Y, Zhang W, Huang Y, et al. Int J Nanomedicine. 2015;10:4043-4057. The Editor and Publisher of the International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of an image in Figure 10 with the same image from Figure 8B in Huang et al, 2016 ‘c(RGDyK)-decorated Pluronic micelles for enhanced doxorubicin and paclitaxel delivery to brain glioma’ (https://doi.org/10.2147/IJN.S104162). Specifically, Figure 10, Heart, F127/P105/MTX appears to have been duplicated with the same image from Figure 8B, Heart, Saline in Huang et al, 2016. The authors responded to our queries and explained that the animal experimental work for both studies was performed at the same time. It was possible an error was made during the arrangement of the H&E images for the respective figures from both articles. However, given the length of time that has passed since the completion of these studies the authors were no longer able to retrieve the original data. To help maintain the integrity of the scientific record the authors agreed with the decision to retract the article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

[Display omitted] • Pluronic-based mixed micelles (hydrophobized using α-linolenic acid) having inherent LAT1 targeting ability (tyrosine-stapled) were developed (LPT T-MM) • IC 50 values for LPT T-MM were significantly reduced in MDA-MB-231 (∼1.64-fold) and 4 T1 (∼1.88-fold) cell lines as compared to LPT. • Apoptosis index were significantly higher in MDA-MB-231 (∼2.04-fold) and 4 T1 cell line (∼2.09-fold) as compared to LPT. • LPT T-MM generated more reactive oxygen species and caused mitochondrial membrane depolarization. The available treatment modalities for triple-negative breast cancer (TNBC) face several challenges, including discouraging overall survival outcomes, unavoidable toxicities, and the emergence of drug resistance. Further, there is an amplified requirement for various amino acids to support the uncontrolled proliferation of TNBC. Hence, targeted therapy for enhancing the treatment of TNBC was explored which encompassed hydrophobized (using α-linolenic acid) Pluronic-based mixed micelles having inherent L-type/Large neutral amino acid transporter 1 targeting (tyrosine-stapled) ability (LPT T-MM). LPT T-MM had optimal size (142.34 ± 30.23 nm), polydispersity index (0.224 ± 0.01), and enhanced drug loading capacity (∼10 %). Transmission electron microscopy confirmed their spherical shape. In vitro release studies showed sustained drug release without hemolysis risk. LPT T-MM had higher cellular uptake and cytotoxicity than free LPT. IC 50 values for LPT T-MM were significantly reduced in MDA-MB-231 (∼1.64-fold) and 4 T1 (∼1.88-fold) cell lines; apoptosis index was superior in MDA-MB-231 (∼2.04-fold) and 4 T1 cell line (∼2.09-fold) compared to free LPT. LPT T-MM generated more reactive oxygen species and caused mitochondrial membrane depolarization, indicating increased cell death by apoptosis. Thus, LPT T-MM had the ability to promote apoptosis, showed promise in enhancing the payload capabilities and targeting in TNBC. [ABSTRACT FROM AUTHOR]