Pluronic L64 Research Articles

Stable O/W emulsions by combining Pluronic L64 and Sodium Alginate

Emulsions play a pivotal role in many industrial fields, including food, pharmaceutics, and cosmetics. This paper explores the simultaneous effects of varying concentrations of Pluronic and Sodium Alginate (Alg), with particular attention to the resulting stability and the rheological properties of the incoming oil-in-water emulsions. Pluronics are used as amphiphilic molecules to stabilize the oil droplet interface, Alg is instead used to increase the viscosity of the suspending medium in a way to slow down droplet coalescence. High shear mixing is used to prepare the emulsions, and rheology and optical microscopy are employed to assess their microstructure. By optimizing both Alg and Pluronic concentrations, emulsions stable up to 90 days are achieved.

Pluronic L121-Chrysin conjugated polymeric micelles of exemestane: Improved synergistic effect, in vitro and in vivo anticancer activity

Hormonal imbalances, particularly those involving estrogen and progesterone, are strongly associated with the development of breast cancer. Exemestane, an irreversible aromatase inhibitor, is used to treat estrogen-positive breast cancer. However, its clinical effectiveness is hampered by poor water solubility and bioavailability. Additionally, relying solely on a single chemotherapeutic agent often leads to poor therapeutic outcomes. Thus, there is a growing interest in the co-delivery of anticancer drugs, especially those of natural origin. In this study, our aim was to develop and optimize micelles for the simultaneous delivery of Exemestane and Chrysin. Exemestane was incorporated into mixed micelles via physical loading, while chrysin was linked to Pluronic L121 to create CHS-L121. Employing the Box-Benken design of experiments, we investigated the impact of polymer concentration on the independent variable. The optimized mixed micelles exhibited a particle size of 33.04 ± 2.62 nm and a polydispersity index of 0.145 ± 0.02. Notably, these micelles demonstrated excellent drug loading (5.2±2.2 %) and entrapment efficiency (89.6±2.5 %). In addition, CHS-EXE-MMs exhibited significant cytotoxicity against the MCF-7 cell line and showed enhanced in vivo anticancer activity in BALB/c mice. In vivo pharmacokinetic studies further revealed improved bioavailability of EXE and CHS through micelles. Our findings highlight the potential of CHS-EXE-MMs as a promising approach in breast cancer therapy.

The Changes in the Conductance of Bilayer Lipid Membranes Caused by Pluronics L61 and F68: Similarities and Differences

The Changes in the Conductance of Bilayer Lipid Membranes Caused by Pluronics L61 and F68: Similarities and Differences

Fine-Tuning the Amphiphilic Properties of Carbosilane Dendritic Networks towards High-Swelling Thermogels.

Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61. The dithiol polymers reacted with carbosilane crosslinkers through UV-initiated thiol-ene coupling (TEC), and the resultant materials were classified as non-swelling networks (for PPG, PLUL31 and PLUL61) and high-swelling hydrogels (for PEG and PLUL35). The hydrogels exhibited thermo-responsive properties, shrinking at higher temperatures, and exhibited an intriguing drug release pattern due to internal nanostructuring. Furthermore, we fine-tuned the dendritic crosslinker, including hydroxyl and azide pendant groups in the focal point, generating functional networks that can be modified through degradable (ester) and non-degradable (triazol) bonds. Overall, this work highlighted the crucial role of the amphiphilic balance in the design of dendritic hydrogels with thermo-responsive behavior and confirmed their potential as functional networks for biomedical applications.

Unbiased particle conformation extraction from scattering spectra using orthonormal basis expansions

A strategy is outlined for quantitatively evaluating the particle density profiles from small-angle scattering spectra of dilute solutions. The approach employs an orthonormal basis function expansion method, enabling the determination of characteristic mass distributions in self-assembled structures without the need for a specific structural model. Through computational benchmarking, the efficacy of this approach is validated by effectively reconstructing the density profile of soft-ball systems with varying fuzziness from their scattering signatures. The feasibility of the method is demonstrated by fitting small-angle neutron scattering data obtained from Pluronic L64 micelles at different temperatures. This proposed approach is both simple and analytical, eliminating the requirement for a presumptive structural model in scattering analysis. The new method could therefore facilitate quantitative descriptions of complex nanoscopic structures inherent to numerous soft-matter systems using small-angle scattering techniques.

Encapsulation of Olive Leaf Polyphenol-Rich Extract in Polymeric Micelles to Improve Its Intestinal Permeability.

In the present study, polymeric micelles were developed to improve the intestinal permeability of an extract of Olea europaea L. leaf with a high content of total polyphenols (49% w/w), with 41% w/w corresponding to the oleuropein amount. A pre-formulation study was conducted to obtain a stable formulation with a high loading capacity for extract. The freeze-drying process was considered to improve the stability of the formulation during storage. Micelles were characterized in terms of physical and chemical properties, encapsulation efficiency, stability, and in vitro release. The optimized system consisted of 15 mg/mL of extract, 20 mg/mL of Pluronic L121, 20 mg/mL of Pluronic F68, and 10 mg/mL of D-α-tocopheryl polyethylene glycol succinate (TPGS), with dimensions of 14.21 ± 0.14 nm, a polydisersity index (PdI) of 0.19 ± 0.05 and an encapsulation efficiency of 66.21 ± 1.11%. The influence of the micelles on polyphenol permeability was evaluated using both Parallel Artificial Membrane Permeability Assay (PAMPA) and the Caco-2 cell monolayer. In both assays, the polymeric micelles improved the permeation of polyphenols, as demonstrated by the increase in Pe and Papp values.

Effects of polymeric surfactants with low HLB values on drug and excipient release from self-emulsifying drug delivery systems

In this study, we evaluated the effects of polymeric surfactants with low hydrophile–lipophile balance values (PSLH) lauryl PEG-8 dimethicone (LP8D) and Pluronic L121 (P121) on drug and excipient release from self-emulsifying drug delivery systems (SEDDS). Valsartan (logKOW 1.5) was used as a model drug, whereas oleic acid (logKOW 7.64) was loaded in SEDDS as a model excipient. Diffusion of valsartan from oil phase to aqueous phase was significantly reduced when adding 5 % LP8D or P121 into the oil phase consisting of isopropyl myristate:Capmul MCM 4:1 m/m. Drug diffusion reached plateau phases after 72 h compared to 3 h in case of the non-PSLH oil phase. Adding 10 % either LP8D or P121 further decreased drug diffusion to aqueous phase. P121 showed a more controlled drug diffusion profile than LP8D at the same loading level. PSLH were loaded in SEDDS preconcentrates at different concentrations in the ranges of 0–15 % LP8D and 0–10 % P121 m/m to yield emulsion with size ∼200 nm and polydispersity index <0.3 upon dilution. The burst release phases from PSLH loaded SEDDS were suppressed and better controlled with higher PSLH loading ratios. The presence of PSLH in the oil phase could increase intermolecular interactions such as hydrogen bonding and London dispersion forces between PSLH and drug or excipient molecules as shown by FTIR difference spectra. Furthermore, PSLH can accumulate at the oil-water interfacial barrier and increase the activation energy level for solute molecules diffusion, i.e. adding 10 % LP8D led to a 3-fold increase in activation energy for oleic acid. Therefore, incorporation of PSLH in SEDDS formulation could be a potential approach to reduce drug diffusion coefficients, enhance drug affinity to oil phase and control drug release rate.

Chemotherapy/anti-inflammatory drug co-delivery system based on ortho ester-modified pluronic L61 for reversing tumor multidrug resistance

The development of multidrug resistance (MDR) in malignant tumors is one of the major obstacles to chemotherapy. Herein, ortho ester-modified pluronic L61 (L61) was prepared and coupled with sulindac (Su) to obtain a polymeric prodrug (Su-OE-L61). Su-OE-L61 was further loaded with doxorubicin (DOX) to give a pH-sensitive nanoparticles (Su-OE-L61/DOX NPs). Compared with ortho ester-free nanoparticles (Su-L61/DOX NPs), Su-OE-L61/DOX NPs could effectively trigger drug release under tumor acidic conditions. In vitro experiments demonstrated that Su-OE-L61/DOX NPs significantly increased intracellular drug concentration and enhanced the cytotoxicity to DOX-resist cells (MCF-7/ADR) through L61-mediated anti-MDR effect and the anti-inflammatory effect of sulindac. In vivo studies revealed that the tumor inhibition rates of Su-OE-L61/DOX NPs reached 83.70 %, which was attributed to the synergistic anti-tumor effect of L61, sulindac and DOX. Overall, the chemo/anti-inflammatory drugs co-delivery system based on ortho ester-modified pluronic showed unique advantages in reversing tumor multidrug resistance.

Cellulose nanocrystal and Pluronic L121-based thermo-responsive composite hydrogels

Cellulose nanocrystal (CNC) is a promising sustainable material with its biocompatibility, high aspect ratio, and mechanical strength. CNC-based systems have potential applications in various fields including biosensors, packaging, coating, energy storage, and pharmaceuticals. However, turning CNC into smart systems remains a challenge due to the lack of stimuli-responsiveness, limitation in compatibility with hydrophobic matrices, and their agglomeration tendency. In this work, a thermo-responsive nanocomposite system is constructed with CNCs and polymersome forming Pluronic L121 (L121), and its phase behavior and mechanical properties are investigated in detail. Two different CNC concentration (4 % and 5 %) is studied by changing the L121 concentration (1–20 %) to understand the effect of unimers and polymersomes on the CNC network. At dilute L121 concentrations (1–5 %), the composite system becomes softer but more fragile below the transition temperature. However, it becomes much stronger at higher L121 concentrations (10–20 %), and a gel network is obtained above the transition temperature. Interestingly, the elastically reinforced CNC gels exhibit greater resistance to microstructural breakdown at large strains due to the soft and deformable nature of the large polymersomes. It is also found that the gelation temperature for hydrogels is tunable with increasing L121 concentration, and the nanocomposite hydrogels displayed thermo-reversible rheological behavior.

An Outer Membrane-Inspired Polymer Coating Protects and Endows Escherichia coli with Novel Functionalities.

A bio-inspired membrane made of Pluronic L-121 is produced around Escherichia coli thanks to the simple co-extrusion of bacteria and polymer vesicles. The block copolymer-coated bacteria can withstand various harsh shocks, for example, temperature, pressure, osmolarity, and chemical agents. The polymer membrane also makes the bacteria resistant to enzymatic digestion and enables them to degrade toxic compounds, improving their performance as whole-cell biocatalysts. Moreover, the polymer membrane acts as an anchor layer for the surface modification of the bacteria. Being decorated with α-amylase or lysozyme, the cells are endowed with the ability to digest starch or self-predatory bacteria are created. Thus, without any genetic engineering, the phenotype of encapsulated bacteria is changed as they become sturdier and gain novel metabolic functionalities.

Different effects of two Poloxamers (L61 and F68) on the conductance of bilayer lipid membranes.

The integral conductance of planar lipid bilayer membranes in the presence of two Poloxamers (Pluronics) L61 and F68 with the same lengths of hydrophobic poly(propylene oxide) blocks and the different lengths of hydrophilic poly(ethylene oxide) blocks increases with an increase in the concentration of both Pluronics; however, the shape of the conductance-concentration curves is super linear for L61 and sublinear for F68. In the presence of both Pluronics, rare discrete current jumps are observed against the background of continuous current. At high concentrations, the I-V curves of membranes with both L61 and F68 became nonlinear at sufficiently low voltages but differed significantly. At voltages greater than 50mV, the conductance of membranes with L61 increased sharply and quantized jumps were observed toward higher conductance, which could be interpreted as the appearance of additional pores. On the contrary, the conductance of membranes with F68 decreased and quantized jumps to lower conductance were observed, which could be interpreted as blocking of already existing pores. We attributed the differences in the conductance-concentration and I-V curves of these two Pluronics to their different effects on the dynamics of membrane hydration and, accordingly, on the probability of formation of conducting pores.

Anion Effects on the Liquid-Liquid Equilibrium Behavior of Pluronic L64 + Water + Sodium Salts at Different pH: Determination of Thermodynamic Parameters

Two-phase aqueous systems have replaced and simplified steps in extraction and purification processes, especially for biocompounds. Thus, this study evaluated the liquid-liquid equilibrium behavior of Pluronic L64 + water + sodium salts at pH 5.0, 7.5, and 10.0. Sodium sulfate demonstrated the greatest phase separation, followed by sodium citrate and sodium tartrate. Higher pH values resulted in larger biphasic regions. The polymer distribution coefficients increased with the addition of salt. As pH increased, there was a tendency for Pluronic L64 to migrate to the polymer-rich phase. The Gibbs energy of micellization between −11,000 and −25,000 kJ mol−1 indicated the spontaneity of the process micellization for all systems, showing lower values for the systems with sodium sulfate. This parameter was related to the anion speciation at each pH. Besides, the effects of water structuring around ions and ion-polymer interaction influenced the phase separation.

Comparative interaction of an anionic dye, ponceau 4R with triple viz., anionic, non-ionic and cationic micellar systems: Spectral and conductometric analysis

In this work, the interaction of ponceau 4R dye (P4R) with triple viz., anionic, nonionic and cationic micellar systems has been studied. The three surfactants employed were nonionic pluronic L-64 (PL-64), anionic sodium dodecyl sulphate (SDS) and cationic cetyl trimethyl ammonium bromide (CTAB). All the three dye - surfactants systems were investigated through UV - visible spectroscopy, conductivity, FT-IR, pH effect and SEM studies. There was short and strong bonding between the dye and all the three types of micelles as observed from FT-IR studies. The conductivity studies displayed greater interaction with CTAB than with SDS. The free energy of micellization, ∆G was observed to be -16.07 kJ mol−1 for P4R+ CTAB and -13.83 kJ mol−1 for P4R + SDS, demonstrating greater spontaneity and stability of the former combination. This can be explained due to strong electrostatic attraction between negatively charged P4R dye and positively charged micelle of CTAB. Overall, the anionic ponceau 4R dye has been successfully incorporated into the nonionic, anionic and cationic micellar systems. This is probably the first report of interaction of a similarly charged dye and surfactant system.

3D-printed surgical wound dressing for prolonged 5-fluorouracil delivery from pluronic blending composites

A direct drug delivery system of with the inhibition of multidrug resistance was developed in this study by the polymer mixing of Pluronic block copolymer F127, L121, polyethylene glycol (PEG), and polyvinyl alcohol (PVA). The polymer mixing was defined as Pluronic blending composites (PBCs) and optimized through adjusting the ratio of two different water-soluble homopolymers, PEG and PVA. The chemotherapeutic drugs of 5-fluorouracil (5-FU) were released from Pluronic blending composites nearly one month without continuous supplementary. Also, the effective ingredient of L121 inhibited multidrug resistance in human pancreatic cancer and caused the malfunction of the ATP binding cassette subfamily C (ABCC) transporter as evidenced by the flow cytometer studies. PBC-3 effectively suppresses the function of ABCC transporter up to 25 days. 5-FU are able to accumulate in the cancer cells of AsPC-1 and PANC-1 at a designated effective concentration. Then, a surgical dressing was prepared by 3D bio-printing technology with Pluronic blending composites cross-linked by sodium alginate. Results show that the surgical dressing of 24 layers with 10 mm × 10 mm would continuously release 5-FU in effective anticancer concentration for six days.

Insights into the Phase Diagram of Pluronic L64 Using Coarse-Grained Molecular Dynamics Simulations.

We investigate the concentration-dependent phase diagram of pluronic L64 in aqueous media at 300 and 320 K using coarse-grained (CG) molecular dynamics (MD) simulations. The CG model is derived by adapting the Martini model for nonbonded interactions along with the Boltzmann inversion (BI) of bonded interactions from all-atom (AA) simulations. Our derived CG model successfully captures the experimentally observed micellar-, hexagonal-, lamellar-, and polymer-rich solution phase. The end-to-end distance reveals the conformational change from an open-chain structure in the micellar phase to a folded-chain structure in the lamellar phase, increasing the orientational order. An increase in temperature leads to expulsion of water molecules from the L64 moiety, suggesting an increase in L64 hydrophobicity. Thermodynamic analysis using the two-phase thermodynamics (2PT) method suggests the entropy of the system decreases with increasing L64 concentration and the decrease in free energy (F) with temperature is mainly driven by the entropic factor (-TS). Further, the increase in aggregation number at lower concentrations and self-assembly at very high concentrations is energetically driven, whereas the change from the micellar phase to the lamellar phase with increasing L64 concentration is entropically driven. Our model provides molecular insights into L64 phases which can be further explored to design functionality-based suprastructures for drug delivery and tissue engineering applications.

Prolonged control of insulin-dependent diabetes via intramuscular expression of plasmid-encoded single-strand insulin analogue

Daily insulin injection is necessary for the treatment of the insulin-dependent diabetes. However, the process is painful and inconvenient. Accordingly, we have made exploratory efforts to establish an alternative method for continuous insulin supply via intramuscular injection of a designed plasmid encoding the single-strand insulin analogue (SIA), which provides safe, effective and prolonged control of insulin-dependent diabetes. To generate a SIA, a short flexible peptide was alternatively introduced into the natural proinsulin to replace its original long and rigid C-peptide. Then, the synthetic promoter SP301 was used to drive potent and specific expression of SIA in skeletal muscle cells. By combining the Pluronic L64 and low-voltage electropulse (L/E), the specialized gene delivery technique was applied to efficiently transfer the constructed plasmid into skeletal muscle cells via intramuscular injection. Through these efforts, a plasmid-based intramuscular gene expression system was established and improved, making it applicable for gene therapy. The plasmid-expressed SIA showed biological functions that were similar to that of natural insulin. A single L/E-pSP301-SIA administration provided sustained SIA expression in vivo for about 1.5 months. In addition, the diabetic mice treated with L/E-pSP301-SIA were much healthier than those with other treatments. This plasmid-based system was safe for the treatment of diabetes and did not cause immune responses or pathological damage. The results confirmed that, in a mouse model, long-term positive effects were achieved by a single intramuscular L/E-pSP301-SIA injection, which consequently provided reliable experimental basis for its clinical application for the treatment of diabetes mellitus with promising prospects.

Effect of drug aceclofenac on physicochemical properties of mixed micellar systems

In this article, the effect of the drug aceclofenac (ACF) on the properties of three mixed micellar systems are studied. The three systems were pluronic L64 + F127 (nonionic-nonionic), pluronic L64 + CTAB (cetyltrimethyl ammonium bromide), (nonionic-cationic) and L64 + SDS (Sodium dodecyl sulphate), (nonionic-anionic) combinations. The physicochemical parameters were characterized by different techniques such as UV visible spectroscopy, FTIR, conductance, DLS, and SEM. The presence of ACF affected the nonionic-ionic mixed micelles more than the nonionic-nonionic group as evidenced by UV spectroscopy. From the DLS measurement, it was observed that ACF enhanced the size of the single micelle of pluronic L64 from 98 to 168 nm. The size of the cationic mixed micelle with ACF displayed 329 nm and the anionic mixed one showed 291 nm suggesting enhanced entrapment efficiency of their mixed micelle compared to the single micelles. The size was also reconfirmed by SEM analysis. From the conductivity measurements of the two nonionic-ionic micellar systems, the counter ion binding constant β, and the thermodynamic parameters ΔG, ΔH, and ΔS were determined. The negative value of ΔG infers spontaneous binding between ACF and ionic mixed micelles.Article highlightsIonic mixed micelles are more effective than nonionic pair.ACF has more spontaneous binding with anionic mixed micelle compared to cationic.The drug entrapment efficiency is better in mixed micelles than in single micelles.

Topology and Sequence-Dependent Micellization and Phase Separation of Pluronic L35, L64, 10R5, and 17R4: Effects of Cyclization and the Chain Ends.

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.

Solvent-Free Formation of Cyclodextrin-Based Pseudopolyrotaxanes of Polyethylene Glycol: Kinetic and Structural Aspects.

Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as “molecular necklaces”. While the synthesis and reaction mechanisms of these structures in solution have been widely described, their solvent-free production has received little attention, despite the advantages that this route may offer. We propose in this work a kinetic mechanism that describes the PPR formation in the solid phase as a process occurring in two consecutive stages. This mechanism has been used to investigate the spontaneous formation of a PPR that occurs when grinding α-Cyclodextrin (α-CD) with polyethylene glycol (PEG). In the threading stage, the inclusion of the polymer and subsequent release of the water molecules lodged in the cavity of the macrocycle cause vibrational changes that are reflected in the time-dependence of the FTIR-ATR spectra, while the further assembly of PPRs to form crystals produces characteristic reflections in the XRD patterns, due to the channel-like arrangement of CDs, that can be used to track the formation of the adduct in crystalline form. The effects that working variables have on the kinetics of the reaction, such as temperature, feed ratio, molar mass of the polymer and the introduction of an amorphous block in the polymer structure, have been investigated. The rate constants of the threading step increase with the temperature and the activation energy of the process increases at lower proportions of CD to PEG. This is attributed to the lower degree of covering of the polymer chain with CDs that reduces the hydrogen-bonding driven stabilization between adjacent macrocycles. The formation of crystalline PPR, which takes place slowly at room temperature, is markedly promoted at higher temperatures, with lower proportions of CD favoring both the formation and the growth of the crystals. The molar mass of the polymer does not modify the typical channel-like arrangement of packed PPRs but the conversion into crystalline PPR diminishes when using PEG1000 instead of PEG400. At a microscopic level, the crystals arrange into lamellar structures, in the order of hundreds of nm, embedded in an amorphous-like matrix. The introduction of a polypropylene oxide block in the structure of the polymer (Pluronic L62) renders poorer yields and a considerable loss of crystallinity of the product of the reaction. The methodology here proposed can be applied to the general case of inclusion complexes of CDs with drugs in the solid phase, or to multicomponent systems that contain polymers as excipients in pharmaceutical formulations along with CDs.

DPD Study on the Interfacial Properties of PEO/PEO-PPO-PEO/PPO Ternary Blends: Effects of Pluronic Structure and Concentration.

Using the method of dissipative particle dynamics (DPD) simulations, we investigated the interfacial properties of PEO/PEO-PPO-PEO/PPO ternary blends composed of the Pluronics L64(EO13PO30EO13), F68(EO76PO29EO76), F88(EO104PO39EO104), or F127(EO106PO70EO106) triblock copolymers. Our simulations show that: (i) The interfacial tensions () of the ternary blends obey the relationship < < < , which indicates that triblock copolymer F68 is most effective in reducing the interfacial tension, compared to L64, F88, and F127; (ii) For the blends of PEO/L64/PPO and the F64 copolymer concentration ranging from ccp = 0.2 to 0.4, the interface exhibits a saturation state, which results in the aggregation and micelle formation of F64 copolymers added to the blends, and a lowered efficiency of the L64 copolymers as a compatibilizer, thus, the interfacial tension decreases slightly; (iii) For the blends of PEO/F68/PPO, elevating the Pluronic copolymer concentration can promote Pluronic copolymer enrichment at the interfaces without forming the micelles, which reduces the interfacial tension significantly. The interfacial properties of the blends contained the PEO-PPO-PEO triblock copolymer compatibilizers are, thus, controlled by the triblock copolymer structure and the concentration. This work provides important insights into the use of the PEO-PPO-PEO triblock copolymer as compatibilizers in the PEO and PPO homopolymer blend systems.