Hydrophilic-lipophilic Balances Research Articles

Stability and characteristics of kerosene-in-water emulsions with xanthate surfactants: Influence of hydrophilic-lipophilic balance and molecular weight

The understanding of emulsion stability is important for several industrial applications including foods, pharmaceuticals, petroleum, personal care products, and in our case mineral processing. Xanthate functional surfactants may be useful to improve mineral recovery through froth flotation by delivering oil to valuable mineral surfaces as they may be used to stabilize kerosene-in-water emulsions. The eco-friendly nature of naturally derived reagents such as vitamin E-based xanthates would be beneficial to the mineral processing industry. In this study, conventional (potassium amyl xanthate (PAX)) and novel xanthate functional surfactants such as α-tocopherol polyethylene glycol 400 succinate (TPGS) xanthates which we synthesized from Vitamin E were investigated as emulsifiers. The creaming and oil phase separation of the kerosene-in-water emulsions produced with the xanthate surfactants were studied. The influence of hydrophilic-lipophilic balances (HLBs) and molecular weights (MWs) of the water-soluble xanthates and other commercial surfactants including polyoxyethylene fatty acid esters (Tweens), sorbitan fatty acid esters (Spans), and polyoxyethylene fatty ethers (Brijs) on the characteristics of the kerosene-in-water emulsions was examined. The experimental results showed that the TPGS xanthate formed the most stable emulsion among the xanthate surfactants considered. The results indicated that HLB is not the only factor influencing the emulsifying properties of surfactants. The chemical structure, particularly the molecular weight of the surfactant has a significant impact on its emulsifying properties. Thus, an emulsion stability chart incorporating the HLB and molecular weight of surfactants is proposed. This stability chart can be used for a better classification of the emulsifying properties of commercially available surfactants and novel reagents.

Surfactant-Dependent Partitioning of Organics in Aqueous-Organic Reaction Systems.

A fluorescence lifetime imaging microscopy (FLIM) technique characterizes surfactant-dependent partitioning of organics in a system that mimics a Negishi-like cross-coupling reaction in water, under synthetic concentrations, with emulsion droplets. Experimental partitioning data were not predictable from simple hydrophilic-lipophilic balances. The ionic surfactant cetrimonium chloride suppressed the reactivity of the metallic zinc surface, presumably through competitive chloride binding and concurrent cetrimonium coating, a finding that may contribute to the reduced performance of ionic surfactants in the bench-scale coupling reaction.

Sucrose Esters as Oleogelators in Mono or Binary Structured Oleogels Using Different Oleogelation Routes.

Sucrose esters (SE) have been investigated as structuring agents in oleogels. Due to the low structuration power of SE as single agent, this component has recently been explored in combination with other oleogelators to form multicomponent systems. This study aimed to evaluate binary blends of SEs with different hydrophilic-lipophilic balances (HLBs) with lecithin (LE), monoglycerides (MGs) and hard-fat (HF), according to their physical properties. The following SEs, SP10-HLB2, SP30-HLB6, SP50-HLB11, and SP70-HLB15, were structured using three different routes: "traditional", "ethanol" and "foam-template". All binary blends were made using a 10% oleogelator in 1:1 proportion for binary mixtures; they were then evaluated for their microstructure, melting behavior, mechanical properties, polymorphism and oil-binding capacity. SP10 and SP30 did not form well-structure and self-standing oleogels in any combination. Although SP50 showed some potential blends with HF and MG, their combination with SP70 led to even more well-structured oleogels, with a higher hardness (~0.8 N) and viscoelasticity (160 kPa), and 100% oil-binding capacity. This positive result might be attributed to the reinforcement of the H-bond between the foam and the oil by MG and HF.

Hydrophobic Modification of Poly(γ-glutamic acid) by Grafting 4-Phenyl-butyl Side Groups for the Encapsulation and Release of Doxorubicin.

The delivery of drugs is a great challenge, since most of active pharmaceutical ingredients developed today are hydrophobic and poorly water soluble. From this perspective, drug encapsulation on biodegradable and biocompatible polymers can surpass this problem. Poly(γ-glutamic acid) (PGGA), a bioedible and biocompatible polymer has been chosen for this purpose. Carboxylic side groups of PGGA have been partially esterified with 4-phenyl-butyl bromide, producing a series of aliphatic-aromatic ester derivatives with different hydrophilic-lipophilic balances. Using nanoprecipitation or emulsion/evaporation methods, these copolymers were self-assembled in a water solution, forming nanoparticles with average diameters between 89 and 374 nm and zeta potential values between -13.1 and -49.5 mV. The hydrophobic core containing 4-phenyl-butyl side groups was used for the encapsulation of an anticancer drug, such as Doxorubicin (DOX). The highest encapsulation efficiency was reached for a copolymer derived from PGGA, with a 46 mol% degree of esterification. Drug release studies carried out for 5 days at different pHs (4.2 and 7.4) indicated that DOX was released faster at pH 4.2, revealing the potential of these nanoparticles as chemotherapy agents.

Effect of W/O pre-emulsion prepared with different emulsifiers on the physicochemical properties of soy protein isolate-based emulsion films

The effects of incorporating a water-in-oil pre-emulsion based on different emulsifiers with similar hydrophilic-lipophilic balances on the physicochemical properties of soy protein isolate-based emulsion films were investigated. Confocal laser scanning microscopy images indicated that the oil droplet size in the polyglycerol polyricinoleate and lecithin pre-emulsions was larger than that in the glycerol monostearate, span, and sucrose ester pre-emulsions. By contrast, the oil droplet size in the film-forming emulsions had opposite orders. After drying, the polyglycerol polyricinoleate and lecithin emulsion films contained small and evenly distributed oil droplets and demonstrated a small difference of upper and lower surfaces in oil concentration and contact angle. The water vapor permeability of emulsion films prepared by polyglycerol polyricinoleate and lecithin pre-emulsion was 2.35 × 10−10 g m−1 s−1 Pa−1 and 2.32 × 10−10 g m−1 s−1 Pa−1, respectively, lower than that of other emulsion films. The control emulsion films had the highest tensile strength of 7.43 MPa, whereas polyglycerol polyricinoleate emulsion films had the lowest tensile strength of 4.87 MPa. Furthermore, the polyglycerol polyricinoleate emulsion films had the lowest glass transition temperature among the prepared emulsion films. This study concluded that the properties of film-forming emulsions could be affected by pre-emulsions based on different emulsifiers, resulting in different physicochemical properties of the emulsion films.

The Use of Sea Buckthorn Processing Products in the Creation of a Functional Biologically Active Food Emulsion.

The current trend in dietary supplements and functional foods is the use of lipophilic bioactive compounds. The sea buckthorn (Hippóphae rhamnoídes) contains some such compounds: polyunsaturated fatty acids, tocopherols, and carotenoids. Lipophilic components are best distributed using oil-in-water emulsions, which ensures their high bioavailability. A significant property of emulsions is colloidal and oxidative stability, so the choice of emulsifiers that have both surface-active properties and antioxidant activity is an important area of research for making new types of food emulsions. The purpose of this study is the development and refinement of an emulsified biologically active food additive containing sea buckthorn products (pulp, juice, and oil) and stabilized with soy phospholipids. We studied the fruits of Chuyskaya, Orange, and Prevoskhodnaya sea buckthorn varieties growing in the Altai Territory. As we analyzed their composition, we chose the Chuyskaya variety for making the emulsion. The fruits contain 5.30 ± 0.1% of lipids including 16.8 ± 0.5 mg/100 g of carotenoids and 10.5 ± 0.5 mg/100 g of tocopherols. To choose the emulsifier we studied the fractional and fatty acid composition of the soy and sunflower phospholipids with different hydrophilic-lipophilic balances (HLB). We made the emulsions containing sea buckthorn oil and pulp of its different layers, soybean oil, and phospholipids by dispersion using an HG-15D homogenizer. The study of the colloidal stability showed that the most stable (99.5%) are the emulsions containing a mixture of hydrolyzed soybean phospholipids (HLB = 7) and fractionated soybean phospholipids (HLB = 3). The best ratio is 40:60. We examined the oxidative stability of the emulsions by provoking accelerated oxidation. The emulsions containing 1.5% of a soy phospholipids mixture showed the best oxidative stability. The resulting direct oil-in-water fine emulsion contains polyunsaturated fatty acids (PUFAs), tocopherols, β-carotene, and essential phospholipids. For this reason, the emulsion can be used to make biologically active food supplements (also encapsulated) and as part of special nutrients.

Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation.

This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer- (PL-) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic-lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G′/G” = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R2 = 0.923–0.989), indicating the drug diffusion from hydrogels to the medium. RVC-PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.

Formulation, Optimization, and Evaluation of Oregano Oil Nanoemulsions for the Treatment of Infections Due to Oral Microbiota.

IntroductionNatural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation’s aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health.MethodsSeveral OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities.ResultsThe NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats.ConclusionThis study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.

Non-ionic Surface Active Agents as Additives toward a Universal Porogen System for Porous Polymer Monoliths.

The influence of the addition of various non-ionic surfactants to poly(ethylene glycol) diacrylate-based monolith formulations was studied. Eight non-ionic surfactants having different chemistries were chosen for this study. These surfactants were Brij L4, Span 80, IGEPAL CO-520, Tergitol 15S9, 2,4,7,9-tetramethyl-5-decyne-4,7-diol ethoxylate, Tween 40, Triton X-405, and Tetronic 701. The chemical structures of these surfactants have a variety of functional groups and cover a wide range of molecular weights (360-3600 g/mol), viscosities (60-1500 cP), and hydrophilic-lipophilic balances (1.0-17.6). The formed polymers were characterized by scanning electron microscopy, surface area measurement by the Brunauer-Emmet-Teller method, elemental analysis, and Fourier transform infrared. Four formulations, involving the use of surfactants, resulted in permeable materials when prepared in 150 μm ID silica capillaries. The chromatographic performance of the resulting columns in reversed-phase mode was evaluated and compared using a mixture of alkyl benzenes as test analytes. The highest efficiency and methylene selectivity were observed when Tween 40 was included in the formulation, using decane/decanol/dodecanol as coporogens. This porogenic mixture was successfully used for preparation of monolithic columns from a selection of methacrylate- and styrene-based monomers, including butylmethacrylate, hydroxyethymethacrylate, laurylmethacrylate, glycidyl methacrylate, bisphenol diacrylate, benzylmethacrylate, and N,N-dimethylacrylamide, as well as for divinylbenzene. These results show the applicability of this porogenic mixture for a variety of monolithic formulations, providing an approach for developing a universal porogen system.

Association Between Fomesafen and Surfactants for the Pre-emergence Control of Euphorbia heterophylla L.

This work was conducted with the objective to determine Euphorbia heterophylla control with fomesafen in association with surfactants applied in pre-emergence, in substrates and soils with different characteristics. Three studies were carried out in pots, conducted in greenhouse, in a completely randomized experimental design. The first two studies consisted of investigating the efficacy of pre-emergence combinations of fomesafen and surfactant in the control of E. heterophylla, applied on different substrates (Study 1) and soils (Study 2) with different textural classes. Study 3 was carried out to evaluate the effect of fomesafen, applied in pre-emergence and in combination with adjuvants with different HLB's (hydrophilic-lipophilic balances). The herbicide efficacy on E. heterophylla and plant shoot dry mass were evaluated. The association of adjuvant to fomesafen, in pre-emergence, reduced plant growth in the different substrates and soils. The fomesafen response was influenced by the addition of surfactants with different HLB's. The increase in organic matter content in substrates or soil was related to the decrease of the effect of the surfactants on the control of E. heterophylla with fomesafen, or the effect was only manifested in higher herbicide dosages. Fomesafen associated with surfactant with HLB of 8.6 provided the highest levels of weed control.

Correlations for Easy Calculation of the Critical Coalescence Concentration (CCC) of Simple Frothers

Can the critical coalescence concentration (CCC) of the flotation frothers be predictable? What is the relation between their molecular structure and their CCC values? A literature survey found specific correlations between the hydrophilic-lipophilic balances (HLB) and HLB/Mw (where Mw stands for the molecular mass) of homologue series of frothers and their CCC values, but the results are invalid when the molecule’s functional groups change. For this reason, 37 frothers with known values of CCC were analyzed. The CCC values of seven frothers were determined, and the rest were taken from the literature. The frothers were subdivided in homologue series with an increasing number of the carbon atoms with an account for the type and the location of the functional group, thus deriving three types of correlations lnCCC = f(HLB) applicable for: (i) alcohols; (ii) propylene glycols alkyl ethers and propylene glycols; (iii) ethylene glycols alkyl ethers. The average accuracy of these correlations between CCC and HLB is 93%.

Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery.

Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid–Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic–lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle–micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G’/G” relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm−2) compared to OA-PL F-127 (3.51 μg.cm−2) and OA (2.25 μg.cm−2) or hydrogels (∼1.2 μg.cm−2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml−1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration.

Tailoring novel soft nano-vesicles ‘Flexosomes’ for enhanced transdermal drug delivery: Optimization, characterization and comprehensive ex vivo – in vivo evaluation

The transdermal route is a convenient non-invasive way for drug delivery, however, the hydrophobic compact nature of stratum corneum (SC) forms an obstacle hindering the diffusion of drugs particularly hydrophilic ones. Hence, the purpose of this study was to develop novel soft nano-vesicles, entitled Flexosomes, amalgamating two penetration enhancers, ethanol and one edge activator (EA) from various types and different hydrophilic-lipophilic balances. The tailored vesicles were loaded with tropisetron hydrochloride (TRO), a potent highly-soluble anti-emetic, and compared with ethosomes. Aiming to preclude the formation of rigid non-deformable mixed micelles, all critical parameters; EA type, phosphatidylcholine-to-EA molar ratio, and cholesterol concentration, were optimized proving their influences on vesicle-to-micelle transitions. The prepared formulations were characterized in terms of visual inspection, particle size, polydispersity, zeta potential, turbidity measurements, entrapment efficiency, and vesicle morphology. The permeation mechanisms were assessed by differential scanning calorimetry on isolated SC. The modified vesicles, based on ethanol and either vitamin E or PEGylated castor oil derivatives exhibited the highest transdermal fluxes confirmed by a deeply tracking to dermis using confocal laser microscopy. Both vesicles demonstrated higher bioavailability relative to ethosomes, topical and oral aqueous solutions. The findings endorsed the effectiveness of tailored nano-vesicles in boosting TRO skin transport suggesting their applicability with various drug entities for enhanced transdermal delivery.

Linear and Cyclolinear Polysiloxanes in the Bulk and Thin Films on Liquid and Solid Substrate Surfaces

The special features of self-organization and structure formation observed at the interface between different-polarity phases of macromolecules with various hydrophilic-lipophilic balances are reviewed by the example of amphiphilic siloxanes: polymers, oligomers, and low-molecular compounds. The structure of polyorganosiloxanes, the peculiarities of their behavior and conformational changes at the phase interface, and the influence of molecular mass, end groups, hydrophobic bulk substituents, chemical structure of the main (linear or cyclolinear) chain, and the subphase on the surface properties of the compounds mentioned above are analyzed.

Nanosuspended branched chain amino acids: the influence of stabilizers on their solubility and colloidal stability.

This study examined the influence of stabilizers with different hydrophilic-lipophilic balances on the solubility of branched chain amino acids (BCAA) and colloidal stability of nanosuspended BCAAs. Initial BCAA solubility increased by homogenization as evidenced by the BCAA solubility in Tween 80-based nanosuspensions, which remained at almost 97% of their initial solubility after 20days of storage. However, the contents of solubilized BCAAs in Span 80-based nanosuspensions decreased to approximately 85% of their initial solubility after 20days of storage. In fact, the BCAA:Tween 80 ratio had no effect on the colloidal stability but the same variable changed according to the BCAA:Span 80 ratio. Based on this study, it can be concluded that stabilizers with a hydrophilic trait (Tween 80) could be more effective in improving BCAA solubility and the colloidal stability of nanosuspended BCAAs compared to those with a lipophilic trait (Span 80).

Amphiphilic Nanoparticle-in-Nanoparticle Drug Delivery Systems Exhibiting Cross-Linked Inorganic Rate-Controlling Domains

Aiming to explore the potential of sol–gel chemistry to physically stabilize polymeric micelles and confer sustained release features, this work reports for the first time on the production of hybrid organic–inorganic multimicellar nanomaterials that, as opposed to the state-of-the-art materials, display cross-linked poly(siloxane) rate-controlling domains. To achieve this goal, poly(ethylene oxide)-b-poly(propylene oxide) amphiphiles with different architectures (linear and branched) and hydrophilic–lipophilic balances were primarily modified with alkoxysilane moieties through the reaction of the terminal hydroxyl groups of the copolymer and 3-(triethoxysilyl)propyl isocyanate. Then, ethoxysilane-modified polymeric micelles were prepared in water where hydrolysis resulted in a silanol-decorated surface that was cured by spray-drying. Because of the singular spraying mechanism of the Nano Spray-Dryer B-90 used in this work, which is based on a vibrating mesh spray with holes in the 4–7 μm size range that ...

Nonionic surfactant structure on the drug release, formulation and physical properties of ethylcellulose microspheres

Evaluate the effects of nonionic surfactants Brij 58 and Tween 40 with different structures but similar hydrophilic lipophilic balances (HLBs) on theophylline (TH)-loaded ethylcellulose (EC) microspheres. Microspheres were formulated using ratios of the surfactants with matching HLB values but different chemical-structures at temperatures (22/35 °C) by hydrophobic solvent-emulsion evaporation. Particle size, GMD, drug loading, encapsulation efficiency and dissolution were evaluated. Drug release was determined using the zero- and first-order, Higuchi and Hixson–Crowell models. EC microspheres prepared with surfactant Brij 58 showed discrete, free-flowing spherical particles, solid interiors and increased particle smoothness as temperature increased; those prepared with Tween 40 appeared porous with coarser surface morphology as temperature increased; both were CHLB (Combined HLB) dependent. Dissolution obeyed the Higuchi model drug release for both microspheres prepared with Tween 40 and Brij 58 except for those prepared with Brij 58 at 35 °C, which presented as zero order. The results were ascribed to the different chemical structure of Brij 58 versus Tween 40 and preparation temperature. Surfactant chemical structure is an unreported processing parameter shown here to be important in microsphere formulation. Brij 58 possesses properties unique to its chemical structure that influence pharmaceutical and molecular biopharmaceutical research.

Surface Enrichment by Conventional and Polymerizable Sulfated Nonylphenol Ethoxylate Emulsifiers in Water-Based Pressure-Sensitive Adhesive

Comparisons of properties are made for pressure-sensitive adhesives (PSAs) generated via emulsion polymerization using both conventional and reactive emulsifiers. The emulsifiers are ammonium salts of sulfated nonylphenol ethoxylates with similar chemical structures and hydrophilic–lipophilic balances. The polymerizable surfactant possesses a reactive double bond at its phenyl ring allowing for participation in free-radical polymerization reactions. Incorporation of the polymerizable surfactant into the adhesive polymer was confirmed via reverse-phase liquid chromatography. Surfactant distributions in PSA films were characterized using confocal Raman microscopy and contact angle measurements. Increasing conventional surfactant concentrations in emulsion polymerization reactions resulted in proportional increases in concentrations at the surfaces of latex-cast films. No surface enrichment of adhesive films was observed when reactive emulsifiers were employed. Variations in measured depth profiles and conta...

Solubilization of hydrophobic alcohols in aqueous Pluronic solutions: investigating the role of dehydration of the micellar core in tuning the restructuring and growth of Pluronic micelles

Pluronics® are considered to be good carriers for poorly water soluble substances on account of their superior solubilization capacity over other ionic and nonionic surfactants. Understanding the influence of these substances on the aggregation characteristics of Pluronics® is therefore of overriding importance. In this manuscript we report dynamic light scattering, small angle neutron scattering, fluorescence and viscometry studies on the effect of adding hydrophobic alcohols viz. hexan-1-ol, octan-1-ol and decan-1-ol to the aqueous solutions of two Pluronics® (P85 and P123) with different hydrophilic–lipophilic balances. Both these Pluronics® exhibit a sphere to rod micellar shape transition with increasing temperature, the dynamics of the transition being significantly slower in the case of P123 because of its higher hydrophobicity and molecular weight. The aim of our studies was to investigate the restructuring and growth of Pluronic® micelles upon addition of hydrophobic alcohols that have applications in fields ranging from personal care/food products to pharmaceutical formulations. The studies show that alcohol induced micellar restructuring and growth for the two Pluronics® slow down as the concentration of alcohol increases and in addition their aqueous solubility decreases progressively from hexan-1-ol to decan-1-ol. These observations, which were manifested by a decreasing rate of sphere to rod micellar growth, have been attributed to more effective dehydration of the micellar core by alcohols with higher levels of solubilization and hydrophobicity. The results thus shed light on the specific role of additive induced dehydration of micellar cores in the restructuring and growth characteristics of micelles, for both hydrophilic (P85) and hydrophobic (P123) Pluronics®.

Downregulation of mdr1 and abcg2 genes is a mechanism of inhibition of efflux pumps mediated by polymeric amphiphiles

The ability of cells to acquire resistance to multiple pharmaceuticals, namely multidrug resistance (MDR), is often mediated by the over-expression of efflux transporters of the ATP-binding cassette (ABC) superfamily; for example P-glycoprotein (P-gp or MDR1), breast cancer resistance protein (BCRP or ABCG2), and multidrug resistance-associated protein MRP1. ABCs pump drug molecules out of cells against a concentration gradient, reducing their intracellular concentration. The ability of polymeric amphiphiles to inhibit ABCs as well as the cellular pathways involved in the inhibition has been extensively investigated. This work investigated for the first time the effect of branched poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamines) on the levels of mRNA encoding for MDR1, BCRP and MRP1, in a human hepatoma cell line (Huh7). Copolymers with a broad range of molecular weights and hydrophilic-lipophilic balances were assayed. Results confirmed the down-regulation of mdr1 and abcg2 genes. Conversely, the mrp1 gene was not affected. These findings further support the versatility of these temperature- and pH-responsive copolymers to overcome drug resistance in cancer and infectious diseases.