Electrically conductive and antimicrobial Pluronic-based hydrogels.

Electrically conductive hydrogels (ECHs) combine the electrical properties of conductive materials with the unique features of hydrogels. They are attractive for various biomedical applications due to their smart response to electrical fields. Owing to their distinctive properties, such as biocompatibility, thermosensitivity and self-assembling behaviour, Pluronics can be adopted for the generation of hydrogels for biomedical applications. Here, innovative self-assembling ECHs holding antimicrobial properties for biomedical applications are developed, providing a full characterization of their macroscopic and microscopic properties. The rheological, morphological, and structural properties of Pluronic F68 (PF68) in the presence of conductive poly(3,4-ethylenedioxythiophene):poly-(styrenesulfonate) (PEDOT:PSS) are studied to optimize the synthesis of novel biocompatible and electrically conductive hydrogels. The addition of silver (Ag) flakes to the aqueous samples of PF68/PEDOT:PSS is used to further enhance the systems electrical conductivity and antimicrobial potency. Aqueous optimal samples with 45 wt% PF68 and different PEDOT:PSS/silver contents are investigated by means of experimental rheology and small-angle X-ray scattering (SAXS), to unveil the influence of both PEDOT:PSS and silver on the phase diagram, macroscopic flow properties, and morphology of the Pluronic-based systems. The presence of PEDOT:PSS and silver flakes endows Pluronic systems with high conductive properties, while preserving the same self-assembly features of PF68 in water. Moreover, the functionalisation with silver flakes confers antimicrobial properties to the ECHs, as demonstrated by growth inhibition of the multi-drug resistant bacterium Staphylococcus aureus. The use of PF68 in this work provides a novel route for the synthesis of innovative ECHs, whose functionalities such as self-assembling behaviour, biocompatibility, conductivity, and bioactivity may inspire future avenues in the biomedical field.

Tailoring micellar nanocarriers for pemetrexed in breast cancer: design, fabrication and in vitro evaluation.

Aim: To investigate the pemetrexed encapsulated polymeric mixed micelles (PMMs) against breast cancer treatment.Methods: We meticulously optimized the formulation and conducted extensive characterizations, including photon correlation spectroscopy for micellization, advanced analytical techniques and in vitro cell line assessments.Results: The PMM exhibited favorable characteristics, with a spherical morphology, hydrodynamic particle size of 19.58 ± 0.89 nm, polydispersity index of 0.245 ± 0.1, and a surface charge of -9.70 ± 0.61 mV. Encapsulation efficiency and drug payload reached 96.16 ± 0.37% and 4.5 ± 0.32%, respectively. Cytotoxicity analysis indicated superior efficacy of the PMM over the drug solution.Conclusion: The PMM formulation exhibited controlled release of the drug, and demonstrated enhanced cytotoxicity against breast cancer cells, highlighting its therapeutic promise.

[Box: see text].

Dynamic Covalent Amphiphilic Polymer Conetworks Based on End-Linked Pluronic F108: Preparation, Characterization, and Evaluation as Matrices for Gel Polymer Electrolytes.

We present the development of a platform of well-defined, dynamic covalent amphiphilic polymer conetworks (APCN) based on an α,ω-dibenzaldehyde end-functionalized linear amphiphilic poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol) (PEG-b-PPG-b-PEG, Pluronic) copolymer end-linked with a triacylhydrazide oligo(ethylene glycol) triarmed star cross-linker. The developed APCNs were characterized in terms of their rheological (increase in the storage modulus by a factor of 2 with increase in temperature from 10 to 50 °C), self-healing, self-assembling, and mechanical properties and evaluated as a matrix for gel polymer electrolytes (GPEs) in both the stretched and unstretched states. Our results show that water-loaded APCNs almost completely self-mend, self-organize at room temperature into a body-centered cubic structure with long-range order exhibiting an aggregation number of around 80, and display an exceptional room temperature stretchability of ∼2400%. Furthermore, ionic liquid-loaded APCNs could serve as gel polymer electrolytes (GPEs), displaying a substantial ion conductivity in the unstretched state, which was gradually reduced upon elongation up to a strain of 4, above which it gradually increased. Finally, it was found that recycled (dissolved and re-formed) ionic liquid-loaded APCNs could be reused as GPEs preserving 50-70% of their original ion conductivity.

Peptonics: A new family of cell-protecting surfactants for the recombinant expression of therapeutic proteins in mammalian cell cultures.

Polymer surfactants are key components of cell culture media as they prevent mechanical damage during fermentation in stirred bioreactors. Among cell-protecting surfactants, Pluronics are widely utilized in biomanufacturing to ensure high cell viability and productivity. Monodispersity of monomer sequence and length is critical for the effectiveness of Pluronics-since minor deviations can damage the cells-but is challenging to achieve due to the stochastic nature of polymerization. Responding to this challenge, this study introduces Peptonics, a novel family of peptide and peptoid surfactants whose monomer composition and sequence are designed to achieve high cell viability and productivity at a fraction of chain length and cost of Pluronics. A designed ensemble of Peptonics was initially characterized via light scattering and tensiometry to select sequences whose phase behavior and tensioactivity align with those of Pluronics. Selected sequences were evaluated as cell-protecting surfactants using Chinese hamster ovary (CHO) cells expressing therapeutic monoclonal antibodies (mAb). Peptonics IH-T1010, ih-T1010, and ih-T1020 afforded high cell density (up to 3 × 107 cells mL-1 ) and viability (up to 95% within 10 days of culture), while reducing the accumulation of ammonia (a toxic metabolite) by ≈10% compared to Pluronic F-68. Improved cell viability afforded high mAb titer (up to 5.5 mg mL-1 ) and extended the production window beyond 14 days; notably, Peptonic IH-T1020 decreased mAb fragmentation and aggregation ≈5%, and lowered the titer of host cell proteins by 16% compared to Pluronic F-68. These features can improve significantly the purification of mAbs, thus increasing their availability at a lower cost to patients.

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.

Emerging Treatment Options of Pluronic in Designing Colloidal Nano and Microcarriers Carriers for Various Therapies.

Poloxamers, commonly known as Pluronics, are a special family of synthetic tri-block copolymers with a core structure made of hydrophobic poly (propylene oxide) chains sandwiched by two hydrophilic poly (ethylene oxide) chains. It is possible to modify the mechanical, bioactive, and microstructural characteristics of Pluronics to simulate the behavior of different types of tissues. Additionally, they are auspicious drug carriers with the capacity to increase therapeutic agent availability and to design nano-drug formulations for various ailments. The nanoformulation composed of Pluronics is more susceptible to cancer cells due to their amphiphilic nature and feature of selfassembling into micelles. Today's expanding poloxamer research is creating new hopes that increase the possibility of new remedies for a brand-new nanomedicine age treatment. This article provides a concise overview of the classification, grading, and attributes of drug delivery systems (DDSs) as well as the potential for Pluronics to create micro and nanocarriers. We subsequently discuss its utility in drug delivery for cancer, gene therapy, anti-infective therapy, antioxidants, anti-diabetic drugs, anti-HIV, Alzheimer's disease, and antimicrobial drugs. This review also highlighted several patented formulations that contain various grades of Pluronics in one or more different ways. The recent findings in fundamental research in the field properly demonstrate the strong interest in these novel pharmaceutical strategies.

Application of Pluronics for Enhancing Aqueous Solubility of Lipophilic Microtubule Destabilizing Compounds on the Sea Urchin Embryo Model.

In screening, the dilution of DMSO stock solution of a lipophilic molecule with an assay medium often causes compound precipitation. To overcome the issue, the application of Pluronics as cosolvents was examined using a phenotypic sea urchin embryo assay that allows for the quick and facile evaluation of the antiproliferative effect together with systemic toxicity. Maximum tolerated concentration values for Pluronics L121, P123, and F127 were 1.4 µM, 8.6 µM, and 39.7 µM, respectively, and correlated directly with their hydrophilicity. Pluronics L121 and P123 suppressed cleavage and blastomeres retained the round shape, unlike hydrophilic Pluronic F127, which induced fertilization envelope creasing and embryo deformation that could be associated with the interaction of hydrophilic PEO units with mucopolysaccharides at the surface of sea urchin embryos. The toxicity of P123, but not of L121 and F127, was temperature-dependent and markedly increased at lower temperatures. CMC values obtained at different temperatures confirmed that the toxic effect of P123 was associated with both unimers and micelles, whereas F127 toxicity was related mainly to micelles. Evaluation using phenotypic sea urchin embryo assay revealed that potent microtubule destabilizers, namely albendazole, diarylisoxazole, and two chalcones, retained antimitotic activity after the dilution of their DMSO or 2-pyrrolidone stock solutions with 1.25% w/v Pluronic P123 or 5% w/v Pluronic F127. It was suggested that Pluronic P123 and Pluronic F127 could be used as cosolvents to improve the solubility of lipophilic molecules in aqueous medium.

Poloxamer-based nanogels as delivery systems: how structural requirements can drive their biological performance?

Poloxamers or Pluronics®-based nanogels are one of the most used matrices for developing delivery systems. Due to their thermoresponsive and flexible mechanical properties, they allowed the incorporation of several molecules including drugs, biomacromolecules, lipid-derivatives, polymers, and metallic, polymeric, or lipid nanocarriers. The thermogelling mechanism is driven by micelles formation and their self-assembly as phase organizations (lamellar, hexagonal, cubic) in response to microenvironmental conditions such as temperature, osmolarity, and additives incorporated. Then, different biophysical techniques have been used for investigating those structural transitions from the mechanisms to the preferential component's orientation and organization. Since the design of PL-based pharmaceutical formulations is driven by the choice of the polymer type, considering its physico-chemical properties, it is also relevant to highlight that factors inherent to the polymeric matrix can be strongly influenced by the presence of additives and how they are able to determine the nanogels biopharmaceuticals properties such as bioadhesion, drug loading, surface interaction behavior, dissolution, and release rate control. In this review, we discuss the general applicability of three of the main biophysical techniques used to characterize those systems, scattering techniques (small-angle X-ray and neutron scattering), rheology and Fourier transform infrared absorption spectroscopy (FTIR), connecting their supramolecular structure and insights for formulating effective therapeutic delivery systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-023-01093-2.

Phase transitions of aqueous solutions of Pluronic F68 in the presence of Diclofenac Sodium.

In recent years, advancements in bioengineering and materials science have witnessed increasing interest in synthetic polymers capable of fulfilling various applications. Owing to their distinctive properties, Pluronics can be used as nano-drug carriers, to deliver poorly water-soluble drugs, and as model systems to study colloidal science by tuning amphiphilic properties. In this work, we investigated the effect of diclofenac sodium on the self-assembly and thermoresponsive crystallization of Pluronic F68 in water solutions, by employing experimental rheology and Nuclear Magnetic Resonance (NMR). We built a complete phase diagram as a function of temperature and concentration for 45 wt% Pluronic F68 with various amounts of diclofenac sodium in water. The morphological transitions were followed as a function of temperature via linear rheology. We extrapolated the transition temperatures - identifying distinct phases - as a function of the drug concentration and proposed an empirical model for their prediction. NMR analysis provided further information on the structural characteristics of the systems, shedding light on the interactions between F68 and diclofenac sodium. Although dealing with a pharmaceutical salt, the study is focused on a colloidal system and its interaction with a binding molecule, that is of general interest for colloidal science.

Pluronic F-68 and F-127 Based Nanomedicines for Advancing Combination Cancer Therapy.

Pluronics are amphiphilic triblock copolymers composed of two hydrophilic poly (ethylene oxide) (PEO) chains linked via a central hydrophobic polypropylene oxide (PPO). Owing to their low molecular weight polymer and greater number of PEO segments, Pluronics induce micelle formation and gelation at critical micelle concentrations and temperatures. Pluronics F-68 and F-127 are the only United States (U.S.) FDA-approved classes of Pluronics and have been extensively used as materials for living bodies. Owing to the fascinating characteristics of Pluronics, many studies have suggested their role in biomedical applications, such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. As a result, various studies have been performed using Pluronics as a tool in nanomedicine and targeted delivery systems. This review sought to describe the delivery of therapeutic cargos using Pluronic F-68 and F-127-based cancer nanomedicines and their composites for combination therapy.

Antifouling Properties of Pluronic and Tetronic Surfactants in Digital Microfluidics.

Fouling at liquid-solid interfaces is a pernicious problem for a wide range of applications, including those that are implemented by digital microfluidics (DMF). There are several strategies that have been used to combat surface fouling in DMF, the most common being inclusion of amphiphilic surfactant additives in the droplets to be manipulated. Initial studies relied on Pluronic additives, and more recently, Tetronic additives have been used, which has allowed manipulation of complex samples like serum and whole blood. Here, we report our evaluation of 19 different Pluronic and Tetronic additives, with attempts to determine (1) the difference in antifouling performance between the two families, (2) the structural similarities that predict exceptional antifouling performance, and (3) the mechanism of the antifouling behavior. Our analysis shows that both Pluronic and Tetronic additives with modest molar mass, poly(propylene oxide) (PPO) ≥50 units, poly(ethylene oxide) (PEO) mass percentage ≤50%, and hydrophilic-lipophilic balance (HLB) ca. 13-15 allow for exceptional antifouling performance in DMF. The most promising candidates, P104, P105, and T904, were able to support continuous movement of droplets of serum for more than 2 h, a result (for devices operating in air) previously thought to be out of reach for this technique. Additional results generated using device longevity assays, intrinsic fluorescence measurements, dynamic light scattering, asymmetric flow field flow fractionation, supercritical angle fluorescence microscopy, atomic force microscopy, and quartz crystal microbalance measurements suggest that the best-performing surfactants are more likely to operate by forming a protective layer at the liquid-solid interface than by complexation with proteins. We propose that these results and their implications are an important step forward for the growing community of users of this technique, which may provide guidance in selecting surfactants for manipulating biological matrices for a wide range of applications.

Water-pluronic-ionic liquid based microemulsions: Preparation, characterization and application as micro-reactor for enhanced catalytic activity of Cytochrome-c.

Microemulsions (µEs), comprising water as polar component, pluronic (normal, L35 and reverse, 10R5) as surfactant and a hydrophobic ionic liquid (HIL) as non-polar component have been prepared and characterized. Owing to higher surface activity, pluronics have promoted the formation of µEs without the use of co-surfactant. Thus prepared µEs have been utilized as nano-reactors for the oxidation of guaiacol in the presence of Cytochrome-c (Cyt-c) at 15, 20, and 25 °C. A 3.2- and 1.3-fold increase in the rate of formation of product of enzymatic catalysis in direct µE (HIL-in-water) with reverse pluronic (10R5) is observed at 15 and 20 °C as compared to that in buffer. However, negligible enzymatic activity is observed in the direct µE formed by normal pluronic (L35). The catalytic activity of Cyt-c decreases in reverse µEs (water-in-HIL) as compared to direct µEs irrespective of the nature of pluronic used. The contrasting nature of nano-interfaces formed by pluronics in µEs and the extent of hydration of these nano-interfaces controlled by temperature exerts varying influence on the catalytic activity of Cyt-c. It is expected that the present work would result in providing a versatile platform for the creation of new IL and pluronic-based µEs for bio-catalytic applications, which have never been reported.

Novel Non-Viral Vectors Based on Pluronic® F68PEI with Application in Oncology Field.

Copolymers composed of low-molecular-weight polyethylenimine (PEI) and amphiphilic Pluronics® are safe and efficient non-viral vectors for pDNA transfection. A variety of Pluronic® properties provides a base for tailoring transfection efficacy in combination with the unique biological activity of this polymer group. In this study, we describe the preparation of new copolymers based on hydrophilic Pluronic® F68 and PEI (F68PEI). F68PEI polyplexes obtained by doping with free F68 (1:2 and 1:5 w/w) allowed for fine-tuning of physicochemical properties and transfection activity, demonstrating improved in vitro transfection of the human bone osteosarcoma epithelial (U2OS) and oral squamous cell carcinoma (SCC-9) cells when compared to the parent formulation, F68PEI. Although all tested systems condensed pDNA at varying polymer/DNA charge ratios (N/P, 5/1−100/1), the addition of free F68 (1:5 w/w) resulted in the formation of smaller polyplexes (<200 nm). Analysis of polyplex properties by transmission electron microscopy and dynamic light scattering revealed varied polyplex morphology. Transfection potential was also found to be cell-dependent and significantly higher in SCC-9 cells compared to the control bPEI25k cells, as especially evident at higher N/P ratios (>25). The observed selectivity towards transfection of SSC-9 cells might represent a base for further optimization of a cell-specific transfection vehicle.

Micro-/Nanofibrillated Cellulose-Based Coating Formulations: A Solution for Improving Paper Printing Quality.

The use of micro-/nanofibrillated celluloses (M/NFCs) is often considered for the enhancement of paper properties, while it is still challenging to use them in lower weight gain coatings. This work explores how they might be used on the paper surface to improve the printing quality. In this regard, M/NFCs were produced using different pre-treatment methods, including mechanical (m-MFC), enzymatic (e-MFC), TEMPO-mediated oxidation (t-NFC) and cationization (c-NFC), and uniform coating formulations were developed through the cooking of starch and M/NFCs simultaneously. The formulations, at 6-8% of total solid concentration, were applied to the paper surface by roll coating, resulting in a dry coating weight of 1.5 to 3 g/m2. Besides M/NFCs, other components such as starch betainate (a cationic starch ester; SB), Pluronics® (a triblock co-polymer), precipitated calcium carbonate (PCC) and betaine hydrochloride (BetHCl) were also used in the M/NFC-based coating formulations to observe their combined influence on the printing quality. The presence of M/NFCs improved the paper printing quality, which was further enhanced by the increase in cationic charge density due to the presence of BetHCl/SB, and also by Pluronics®. The cationic charge of c-NFC was also found to be effective for improving the gamut area and optical density of coated papers, whereas whiteness was often reduced due to the quenching of the brightening agent. BetHCl, on the other hand, improved the printing quality of the coated papers, even though it was more effective when combined with M/NFCs, PCC and Pluronics®, and also helped to retain paper whiteness.

Cytocompatibility of Pluronics F-127 on adenocarcinomic human alveolar basal epithelial cells (A549 cells).

Pluronics, due to its high water-soluble and thermoreversible ability, attracted much in biomedical applications. They are mainly utilized in drug delivery, gene therapy, and tissue remodeling. The study aims to explore the cytocompatibility of Pluronics F-127, which has gained much popularity due to its various properties. The cells were exposed to varying concentrations of Pluronics F-127 in A549 cells for 24 h. According to the MTT and neutral red assay, A549 cells displayed dose-dependent cell viability. The cell's morphology was preserved after treatment, as seen in phase-contrast and Giemsa staining. When exposed to PF-127, lysosomal, cytoskeletal, and nuclear integrity were maintained. The percentage of live cells in all the treated groups was more significant than 90%, according to the live/dead flow cytometric analyses. The study identified the cytocompatibility of Pluronics F-127 required for the breakthrough in biomedical applications.

Advances in the therapeutic delivery and applications of functionalized Pluronics: A critical review.

Pluronic (PEO-PPO-PEO) block copolymers can form nano-sized micelles with a structure composed of a hydrophobic PPO core and hydrophilic PEO shell layer. Pluronics are U.S. Food and Drug Administration approved polymers, which are widely used for solubilization of drugs and their delivery, gene/therapeutic delivery, diagnostics, and tissue engineering applications due to their non-ionic properties, non-toxicity, micelle forming ability, excellent biocompatibility and biodegradability. Although Pluronics have been employed as drug carrier systems for several decades, numerous issues such as rapid dissolution, shorter residence time in biological media, fast clearance and weak mechanical strength have hindered their efficacy. Pluronics have been functionalized with pH-sensitive, biological-responsive moieties, antibodies, aptamers, folic acid, drugs, different nanoparticles, and photo/thermo-responsive hydrogels. These functionalization strategies enable Pluronics to act as stimuli responsive and targeted drug delivery vehicles. Moreover, Pluronics have emerged in nano-emulsion formulations and have been utilized to improve the properties of cubosomes, dendrimers and nano-sheets, including their biocompatibility and aqueous solubility. Functionalization of Pluronics results in the significant improvement of target specificity, loading capacity, biocompatibility of nanoparticles and stimuli responsive hydrogels for the promising delivery of a range of drugs. Therefore, this review presents an overview of all advancements (from the last 15 years) in functionalized Pluronics, providing a valuable tool for industry and academia in order to optimize their use in drug or therapeutic delivery, in addition to several other biomedical applications.

Formulation, Characterization and Cytotoxicity Effects of Novel Thymoquinone-PLGA-PF68 Nanoparticles.

Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone's (TQ) biological activity before reaching the target sites. Synthesis of nanoparticles was successfully completed by encapsulating TQ with polymeric poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol) and Pluronics F68 (TQ-PLGA-PF68) using an emulsion-solvent evaporation technique. The size and encapsulation efficiency of TQ-PLGA-PF68 nanoparticles were 76.92 ± 27.38 nm and 94%, respectively. TQ released from these encapsulants showed a biphasic released pattern. Cytotoxicity activity showed that tamoxifen-resistant (TamR) MCF-7 breast cancer cells required a higher concentration of TQ-PLGA-PF68 nanoparticles than the parental MCF-7 cells to achieve IC50 (p < 0.05). The other two resistant subtypes (TamR UACC732 inflammatory breast carcinoma and paclitaxel-resistant (PacR) MDA-MB 231 triple-negative breast cell line) required a lower concentration of TQ-PLGA-PF68 nanoparticles compared to their respective parental cell lines (p < 0.05). These findings suggest that TQ encapsulation with PLGA-PEG and Pluronics F68 is a promising anti-cancer agent in mitigating breast cancer resistance to chemotherapeutics. In future studies, the anti-cancer activity of TQ-PLGA-PF68 with the standard chemotherapeutic drugs used for breast cancer treatment is recommended.

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 (γ) of the ternary blends obey the relationship γF68 < γL64 < γF88 < γF127, 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.

Anti-Aß-scFv-loaded polymeric nano-micelles with enhanced plasma stability.

OBJECTIVES: Immunotherapy using recombinant monoclonal antibodies specifically Anti-amyloid-beta (Anti-Aß) scFv is envisaged as an appropriate therapeutic for Alzheimer through reduction of amyloid-beta aggregation. The solubilization of therapeutics using polymeric micelles facilitates an improved bioavailability and extended blood half-life. In this study, the optimum production condition for Anti-amyloid-beta (Anti-Aß) scFv was obtained. To increase the stability of plasma, Anti-Aß-loaded polymeric micelles were synthesized. METHODS: Escherichia coli SHuffle expression strain was used and purified by Ni-NTA. Pluronics P85 and F127 micelles were used for the Anti-Aß delivery and were characterized in terms of morphology, drug loading and drug release in phosphate buffer and artificial cerebrospinal fluid. The stability profile was quantified at 4°C over a 30 days storage period. The stability in human plasma was also evaluated. KEY FINDINGS: Proteins expressed in SHuffle resulted in increased levels of protein expression and solubility. Low critical micelle concentration value and high micelle encapsulation efficiency (<200 nm) achieved via direct dissolution method. Anti-Aß-loaded micelles were around 2.2-fold more stable than Anti-Aß in plasma solution. A sustained in-vitro release of Anti-Aß from micelles was observed. CONCLUSIONS: Results confirmed that Pluronic-micelles pose benefits as a nano-carrier to increase the stability of Anti-Aß scFvin in the plasma.

Cubosomes enhance drug permeability across the blood-brain barrier in zebrafish.

The potential of cubosomes to improve delivery of incorporated cargo to the brain was explored in zebrafish. Cubosomes were formulated with one of three stabilisers, Pluronic F68, Pluronic F127 or Tween 80, with the hypothesis that coating with Tween 80 will enable brain targeting of cubosomes as has been previously shown for polymeric nanoparticles. The physiochemical properties and the ability of the cubosomes to facilitate delivery of the model drug lissamine rhodamine (RhoB) into the brain was investigated. Distribution of cubosomes in the midbrain was also investigated by ultrastructural analysis via incorporation of octanethiol-functionalized gold nanoparticles. Cubosomes were typically 165-195 nm in size with a Pn3m (Pluronics) or Im3m (Tween 80) cubic phase internal structure. Cubosomes were injected intravenously into zebrafish larvae (12-14 days post fertilization) and the concentration of RhoB in the midbrain was determined by quantifying its fluorescence intensity. Uptake of RhoB was significantly greater in larvae injected with Tween 80 stabilized cubosomes as compared to a control suspension of RhoB or cubosomes stabilized with Pluronics. Collectively, we show for the first time that cubosomes can be functionalized to deliver drug across the BBB, offering new opportunities to overcome drug delivery issues across this formidable biological barrier.