Hydrophobically Modified Hydroxyethyl Cellulose Research Articles

Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification

Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1mol% of hydrophobic groups, while 2mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4°C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4°C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4°C or in the release at 35°C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1mol% HM).

Polymer coated liposomes for use in the oral cavity – a study of the in vitro toxicity, effect on cell permeability and interaction with mucin

In this study we investigated the in vitro toxicity, impact on cell permeability and mucoadhesive potential of polymer-coated liposomes intended for use in the oral cavity. A TR146 cell line was used as a model. The overall aim was to end up with a selection of safe polymer coated liposomes with promising mucoadhesive properties for drug delivery to the oral cavity. The following polymers were tested: chitosan, low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), amidated pectin (AM-pectin), Eudragit, poly(N-isopropylacrylamide-co-methacrylic acid) (p(NIPAAM-co-MAA)), hydrophobically modified hydroxyethyl cellulose (HM-HEC), and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). With chitosan as an exception, all the systems exhibited no significant effect on cell viability and permeability at the considered concentrations. Additionally, all the formulations showed to a varying degree an interaction with mucin (BSM type I-S); the positively charged formulations exhibited the strongest interaction, while the negatively and neutrally charged formulations displayed a moderate or low interaction. The ability to interact with mucin makes all the liposomal formulations promising for oromucosal administration. Although the chitosan-coated liposomes affected the cell viability, this formulation also influenced the cell permeability, which makes it an interesting candidate for systemic drug delivery from the oral cavity.

A dynamic light scattering study of hydrogels with the addition of surfactant: a discussion of mesh size and correlation length

We report a study of the interaction of sodium dodecyl sulfate (SDS) with hydrogels made of hydroxyethylcellulose (HEC) and hydrophobically modified hydroxyethylcellulose (HMHEC) by means of dynamic light scattering. The results reveal that the interaction between the hydrogels and SDS only affects the cooperative diffusion, while the slow relaxation of the hydrogels was not influenced by the interaction. Gel swelling due to the presence of SDS is also examined by measuring the weight change of the gel. The main observation is that when the gel swells due to increasing SDS concentration, the cooperative diffusion becomes faster. As such, we raise the question of whether the correlation length obtained from DLS is still proportional to the mesh size inferred from gel swelling. In the discussion, we attribute the cause to the quantity of bound surfactants. The mutual diffusion of SDS micelles could be detected at high SDS concentrations, and the diffusion coefficient of SDS in the gel matrix was determined. HEC (or HMHEC) gel swells due to increasing SDS concentration, while the cooperative diffusion becomes faster. This indicates that the HEC (or HMHEC) gel can swell until the osmotic pressure equals the modulus when the charge effect dominates over the effect of configurational entropy for uncharged gels interacting with charged surfactants.

Stabilization of Pluronic Gels by Hydrophobically Modified Hydroxyethylcellulose

Hydrophobically modified hydroxyethylcellulose (HM-HEC) of different hydrophobicity has been used to stabilize pluronic gels against dissolution in an aqueous environment. While pluronic by itself dissolves within 1–2 days, the addition of HM-HEC can stabilize part of the gels from dissolving for a period of at least six months. A larger fraction of the gel remains undissolved when utilizing high HM-HEC concentrations and when the degree of hydrophobic modification is increased. The stabilization against fast dissolution makes these systems interesting for drug delivery purposes. The effect of HM-HEC addition on rheological properties of pluronic gels has also been examined. For a low pluronic concentration, the addition of HM-HEC increases the viscosity of the sample, shifts the gel transition to a lower temperature, and reduces the deviscosification of the pluronic gels at high temperatures. When the pluronic concentration is increased, the addition of HM-HEC only affects the sample viscosity at low temperatures.

Monitoring of macromolecular dynamics during a chemical cross-linking process of hydroxyethylcellulose derivatives by dynamic light scattering

We report a study where we follow a chemical crosslinking process and record the intensity autocorrelation functions for two polymer systems, hydroxyethylcellulose (HEC) and hydrophobically modified hydroxyethylcellulose (HMHEC), by dynamic light scattering (DLS). Due to the distinct chemical structures, the measured intensity autocorrelation function shows significant difference between the two systems. Two relaxation modes were found for both systems, which were attributed to the cooperative relaxation and the structural relaxation. The decay rate for cooperative diffusion was found to decrease during the gelation for HEC, but it remains constant for HMHEC. The same trend was found for the structural relaxation where the decay rate decreased as a function of the gelation time for HEC, but not for HMHEC. By analyzing the amplitudes of both relaxation modes, we also found that during the gelation the structural relaxation was suppressed, which was caused by the decrease of the elastic modulus.

Salak Plum Peel Extract as a Safe and Efficient Antioxidant Appraisal for Cosmetics

The antioxidant activities of Salak plum (Salacca edulis) peel extracts were assessed by 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothaiazoline)-6-sulfonic acid (ABTS), and ferric reducing ability of plasma (FRAP) assays. The ethyl acetate (EtOAc) fraction was the most potent (DPPHIC50=2.932 ± 0.030 µg/mL, ABTSIC50=7.933 ± 0.049 µg/mL, FRAPEC=7,844.44 ± 40.734). Chlorogenic acid was detected as the marker (1.400 ± 0.102 g/kg). The EtOAc fraction was non-cytotoxic in vero and normal human fibroblast (NHF) cells. It exhibited cellular oxidative prevention and damage treatment at 5-40 µg/mL in NHF cells. Salak plum peel loaded liposome consisting of lecithin and hydrophobically modified hydroxyethylcellulose (HMHEC) was developed and found stable with adequate entrapment efficacy. Thus Salak plum peel was highlighted as a potential ecological antioxidant for health promotion aspects, and for cosmetics.

Improvement of Mechanical Properties of Noil Hemp Fiber Reinforced Polypropylene Composites by Resin Modification and Fiber Treatment

The present study aims to improve the reinforcement of hemp fibre to polypropylene (PP) by simple resin modification and fibre treatment. Maleic anhydride grafted polypropylene (MAPP) was used as resin modifier by direct mixing with PP, and hydrophobically modified hydroxyethyl cellulose (HMHEC) was used as fibre treatment reagent by immersing fibre into its aqueous solution. The influences of fibre content, resin modification, and fibre treatment on the mechanical properties (tensile, flexural, and impact strengths) of composites were investigated. The change of interfacial bonding between fibre and resin in composites caused by MAPP and HMHEC was studied by scanning electron microscopy and dynamic mechanical analysis. Resin modification and fibre treatment were effective to enhance the mechanical properties of the composites. The improvement in interfacial bonding is quantitatively evaluated with adhesion factor.

Carbohydrate−Protein Interactions Investigated on Plastic Chips Statically Coated with Hydrophobically Modified Hydroxyethylcellulose

We developed a novel method for rapid screening of carbohydrate-protein interactions using poly(methyl methacrylate) (PMMA) channels statically coated with hydrophobically modified hydroxyethylcellulose (HM-HEC). We found that a self-assembled monolayer (SAM) of HM-HEC on a PMMA surface intact by water allows rapid and reproducible separations of glycan samples using a 20 mM phosphate without HM-HEC. The underlying mechanism for dynamic and static coatings on the PMMA surface is discussed. Simultaneous analysis of the molecular interaction between a complex mixture of carbohydrates from alpha1-acid glycoprotein and proteins has been successfully achieved in PMMA channels statically coated with a SAM of HM-HEC.

Single Molecular Pair Interactions between Hydrophobically Modified Hydroxyethyl Cellulose and Amylose Determined by Dynamic Force Spectroscopy

Interactions among HMHEC (hydrophobically modified hydroxyethyl cellulose) and between HMHEC and amylose were investigated by means of dynamic force spectroscopy of single molecular pairs. The technique was realized using a scanning probe based platform, and the molecular pair interactions were investigated in aqueous solutions over a range of force loading rates. Both hydrophobic interactions among hydrophobe C(16) alkyl side chains in HMHEC and association between these hydrophobes in HMHEC and amylose showed a stretching type peak. The distribution analysis of rupture force based on Bell-Evans's model revealed that the peaks had a most probable rupture force ranging from 27 pN at a force loading rate r(f) = 0.43 nN/s to 125 pN at r(f) = 170 nN/s for HMHEC-HMHEC, and from 13 pN at r(f) = 0.20 nN/s to 34 pN at r(f) = 33.7 nN/s for HMHEC-amylose interactions. The distance of the energy barrier relative to the minimum, x(beta), and the apparent lifetime in the absence of external force, tau, were found to depend on the force loading rate, and the average values are estimated to be 0.99 nm and 0.89s for HMHEC-HMHEC and 0.31 nm and 0.075s for HMHEC-amylose interactions. The obtained data for these pairwise molecular interactions are underpinning the associative behavior of the macroscopic properties of aqueous solutions of these polysaccharides.

Spontaneous Adsorption on a Hydrophobic Surface Governed by Hydrogen Bonding

Spontaneous adsorption from solution onto solid surface is a common phenomenon in nature, but the force that governs adsorption is still a matter of considerable debate. (1, 2) We found that surfactants and cellulose adsorb from solution onto a poly(methyl methacrylate) (PMMA) surface in an ordered and cooperative way governed by hydrogen bonding. The glucose rings of n-dodecyl-beta-D-maltoside (DDM) and hydroxyethylcellulose (HEC) stand perpendicular to the surface, H-bond to the surface COOMe groups with their C=O and Me-O bonds parallel to the surface, and form a tight monolayer. The non-H-bonded COOMe groups orient their C=O bonds perpendicular to the surface. In contrast, the glucose rings of hydrophobically modified hydroxyethylcellulose (HMHEC) lie flat with the side chains perpendicular to the surface and H-bond to the perpendicular-oriented C=O groups. The non-H-bonded COOMe groups orient their C=O bonds parallel but Me-O bonds near-perpendicular to the surface for stabilizing HMHEC. The current work provides a detailed picture of how surface-active molecules interact with a solid surface and self-assemble into greatly different architectures.

Microviscosity of hydrophobically modified hydroxyethyl cellulose aqueous solutions

The microviscosity of hydrophobically modified hydroxyethyl cellulose (HMHEC) aqueous solutions is experimentally determined by conductometry with added ions as probe. Compared to its bulk viscosity, the microviscosity of HMHEC solution could be lower by four orders of magnitude. Since the electric conductivity reduction of added NaCl is almost the same for HMHEC and its unmodified counterpart at an equal weight concentration, one can conclude that the hydrophobic modification for the polymer hardly has any effect on the solution's microviscosity.

Effects of β-cyclodextrin and β-cyclodextrin polymer addition and temperature on the modulation of hydrophobic interactions in aqueous solutions of two hydrophobically modified biopolymers

Novel information about the effects of temperature and addition of hydroxypropyl-β-cyclodextrin (HP-β-CD) or a charged β-cyclodextrin polymer (poly(β-CDN +)) on the rheological features of aqueous solutions of hydrophobically modified hydroxyethylcellulose (HM-HEC) and hydrophobically modified dextran (HM-dextran) is given. The viscosity results for the HM-HEC/poly(β-CDN +) system demonstrated that the addition of this cosolute sets up bridges between adjacent polymer chains, which lead to a strong enhancement of the viscosity. Furthermore, a shear thickening effect is registered at fairly high shear rates, and this feature is influenced by temperature. On the other hand, addition of HP-β-CD monomers to the system generates decoupling of associations via inclusion complex formation with the polymer hydrophobic tails. For the HM-dextran solutions, the interaction with the cosolutes is weak and only a slight increase of the viscosity by addition of poly(β-CDN +) is observed. In contrast to the HM-HEC solutions, addition of HP-β-CD monomers to the aqueous solutions of HM-dextran deactivates the intramolecular hydrophobic associations and thereby the compact coil structure expands and this leads to viscosity enhancement. Elevated temperature induces higher chain mobility and the formation of weaker network associations. The bridges formed in the HM-HEC/poly(β-CDN +) system are especially sensitive to temperature changes.

Nonlinear rheology of aqueous solutions of hydrophobically modified hydroxyethyl cellulose with nonionic surfactant

Shear thickening and strain hardening behavior of hydrophobically modified hydroxyethyl cellulose (HMHEC) aqueous solutions was experimentally examined. We focused on the effects of polymer concentration, temperature, and addition of nonionic surfactant. It is found that HMHEC shows stronger shear thickening at intermediate shear rates in a certain concentration range. In this range, the zero-shear viscosity scales with polymer concentration as η 0 ∼ c 5.7 , showing a stronger concentration dependence than for more concentrated solutions. The critical shear stress for complete disruption of the transient network follows τ c ∼ c 1.62 in the concentrated regime. Dynamic tests of the transient network on addition of surfactants show that the enhanced zero-shear viscosity is due to an increase in network junction strength, rather than their number, which in fact decreases. The reduction in the junction number could partly explain the weak variation of strain hardening extent for low surfactant concentrations, because of longer and looser bridging chain segments, and hence lesser nonlinear chain stretching.

Oil-in-water emulsions stabilized by hydrophobically modified hydroxyethyl cellulose: Adsorption and thickening effect

The preparation and stability of oil-in-water emulsions stabilized by hydrophobically modified hydroxyethyl cellulose (HMHEC) were investigated. The rheological measurements of aqueous HMHEC were studied. It was found that HMHEC showed much better thickening ability than the parent (HEC) from which it was derived, which is caused by the association of the hydrophobic alkyl chains, which are absent in HEC. The oscillatory experimental results of the emulsions showed that at higher concentrations, HMHEC could form an elastic gel, which has good thixotropic properties. The stability and droplet size distribution were investigated by visual observation, photomicrograph and a laser-scattering particle size distribution analyzer. The adsorption of HMHEC at the oil–water interface and the surface of emulsion droplets due to the penetration of the alkyl chains in HMHEC into the oil phase were confirmed by visual observation, the interfacial tension method and an in situ environmental scanning electron microscope (ESEM). The stability of emulsions prepared using HMHEC is based on both an associative thickening mechanism caused by alkyl chains in HMHEC and the adsorption of HMHEC at the oil–water interface, which can form a solid film preventing coalescence of the droplets.

Phase behavior and shear thickening of HM-HEC solutions with addition of nonionic surfactant C12E5

An experimental study was carried out to investigate phase and flow behavior of hydrophobically modified hydroxyethyl cellulose (HMHEC) solution with or without nonionic surfactant C12E5. Shear thickening behavior is observed at moderate shear rates for pure HMHEC solutions at modest concentrations. Shear thickening becomes less significant with increasing temperature and disappears at temperature reaching 25 °C for 0.2%(mass fraction) HMHEC. Also, the shear rate at which the maximum viscosity occurs increases with temperature. Addition of a very small amount of C12E5, even below its critical micellar concentration, can promote the thickening and the strongest thickening occurs at around 6×10−5(mass fraction) C12E5. A further addition, however, can suppress the thickening phenomenon that eventually disappears at high enough C12E5 concentrations. It therefore implies that when the surfactant reaches a certain amount and starts to weaken the gel strength, the imposed flow can no longer enhance the networking. While the pure HMHEC solutions always remain a single phase, phase separation takes place for polymer-surfactant mixtures when the C12E5 concentration exceeds about 1.5×10−4.

Clouding and Phase Behavior of Nonionic Surfactants in Hydrophobically Modified Hydroxyethyl Cellulose Solutions

Clouding phenomena and phase behaviors of two nonionic surfactants, Triton X-114 and Triton X-100, in the presence of either hydroxyethyl cellulose (HEC) or its hydrophobically modified counterpart (HMHEC) were experimentally studied. Compared with HEC, HMHEC was found to have a stronger effect on lowering the cloud point temperature of a nonionic surfactant at low concentrations. The difference in clouding behavior can be attributed to different kinds of molecular interactions. Depletion flocculation is the underlying mechanism in the case of HEC, while the chain-bridging effect is responsible for the large decrease of cloud point for HMHEC. Composition analyses for the formed macroscopic phases were carried out to provide support for associative phase separation for the case of HMHEC, in contrast to segregative phase separation for HEC. An interesting three-phase-separation phenomenon was reported in some HMHEC/Triton X-100 mixtures at high surfactant concentrations.

Design and Characterisation of Poly(lactide-co-glycolide) Small Particulate Systems for the Delivery of Immunostimulant CpG Oligonucleotide

The aim of this study was to develop and characterize biodegradable small particles of poly(lactide-co-glycolide) (PLGA) as oral vehicle for immunostimulatory oligonucleotide (ODN-CpG). Three different polymers were used as surface stabilizing agents (SSA): polyvinyl alcohol (PVA), hydrophobically modified hydroxyethylcellulose (HMHEC), or polyethylenimine (PEI). Particle surface was characterized as well as ODN-CpG release kinetics. All particles were found to be around 1 microm. Particles of PLGA-PVA and PLGA-HMHEC were spherical in shape with a smooth surface whereas PLGA-PEI particles were porous. The presence of ODN-CpG within the particle matrix was confirmed in all particle type using scanning laser confocal microscopy. Particle surface assayed by XPS, zeta potential analysis, and evaluation of particle surface hydrophobicity suggested that a significant amount of SSA remains associated onto particle surface. Release profiles evidenced that ODN-CpG release was strongly dependent on particle surface properties. 100% of encapsulated ODN-CpG was released from PLGA-PVA and PLGA-HMHEC particles 37 days after incubation in a buffer solution, whereas only 25% were released from PLGA-PEI particles. ODN-CpG can therefore be nicely entrapped in several types of small particles displaying a prolonged and controlled release upon time. In addition, particle surface is not modified by the presence of ODN-CpG.

Characterization of Interactions in Aqueous Solutions of Hydroxyethylcellulose and Its Hydrophobically Modified Analogue in the Presence of a Cyclodextrin Derivative

The formation of associative networks in semidilute aqueous solutions of hydrophobically modified hydroxyethylcellulose (HM-HEC) is dependent on intermolecular hydrophobic interactions. Addition of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) monomers to the system provides decoupling of these associations via inclusion complex formation with the polymer hydrophobic tails. Results from viscosity, polymer NMR self-diffusion, and dynamic light scattering (DLS) measurements show that the hydrophobic interactions in HM-HEC solutions are effectively suppressed when the level of HP-beta-CD addition increases. Small-angle neutron scattering (SANS) results reveal that the large-scale association complexes in HM-HEC solutions are strongly diminished when the concentration of HP-beta-CD rises. The time correlation data obtained from the DLS experiments unveiled the existence of two relaxation modes: one single exponential at short times followed by a stretched exponential at longer times. The fast mode is always diffusive, whereas the slow mode exhibits progressively stronger wavevector dependence as the intensity of the hydrophobic interactions increases. This feature, as well as the accompanying drop of the stretched exponential beta as the HP-beta-CD concentration decreases, is attributed to enhanced hydrophobic interactions and can be well rationalized in the framework of the coupling model of Ngai.

A study on the solution behavior of IPBC‐hydrophobically‐modified hydroxyethyl cellulose

AbstractThrough the macromolecule reaction method, a series of 4‐isopropylbenzyl chloride (IPBC) hydrophobically‐modified hydroxyethyl cellulose (HAHEC) were synthesized. The use of suitable amount of hydrophobic monomer can ensure both the strong intermolecular association and good water‐solubility of HAHEC. Effects of polymer concentration, shear rates, temperature, and electrolytes on the solution behavior of HAHEC were comprehensively studied, which indicated that the polymers show high viscosification property, excellent viscosity retention in brine water, and surface activity. FTIR, DSC, and UV measurements were applied to characterize the molecular structure and composition of HAHEC to confirm the incorporation of hydrophobic group into the polymer chain. Atomic force microscope (AFM) and fluorescence spectrum measurements were applied to study the formation of the molecule aggregation and hydrophobic microdomain of HAHEC, and revealed the close relationship between the rheological behaviors and the hydrophobic viscosification effect. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2824–2831, 2006

Gels of Hydrophobically Modified Hydroxyethyl Cellulose Cross-Linked by Amylose. Competition with Cyclodextrin

Previous work has shown that amylose (AM) can cross-link hydrophobically modified polymers by inclusion complexation, whereby thermoreversible cold-setting gels are formed. In this work, the competition between AM and cyclodextrin (CD) for the formation of inclusion complexes with hydrophobically modified hydroxyethyl cellulose (HMHEC) is investigated. A detailed study of viscosity, NMR self-diffusion, and chemical shifts of the two-component mixture, CD and HMHEC, was performed. The results imply that 2:1 (CD:polymer hydrophobe) complexes may be formed. The three-component mixtures, HMHEC/AM/CD, were investigated by rheology, NMR self-diffusion, and intensities of the NMR resonance peaks. The CD molecules competed efficiently with the AM molecules, as seen by a decreased storage modulus, an increased self-diffusion of AM and HMHEC, and increased NMR intensities of the HMHEC hydrophobes, as the concentration of CD increased in the solution. A high concentration of CD is needed in the mixtures to inhibit all interactions between HMHEC and AM, and it was shown that there still is an effect of AM at excess CD concentration in the mixtures.