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Fungal β-glucans are compounds with the potential to activate the innate immune system, in part through binding to the receptor dectin-1. In the present study, small-scale methods for preparing dectin-1a binding microparticles from Albatrellus ovinus alkali-soluble β-glucans were investigated. Mechanical milling was time-consuming and yielded large particles with wide size distributions. Precipitation was more successful: the β-glucan was dissolved in 1 M NaOH, diluted, and precipitated in 1:1 mol equiv HCl. This yielded particles in sizes ranging from 0.5–2 μm. The dectin-1a binding activity was determined using HEK-Blue reporter cells. The prepared particles were able to bind to dectin-1a to the same extent as baker’s-yeast-derived β-glucan particles. The precipitation method was convenient as a quick method for small-scale preparation of β-glucan microparticle dispersions from mushroom β-glucans.

Medical use of hydrogen gas (H2) has been given increasing attention over the past 15 years with numerous clinical trials for a variety of indications. The biological activity of H2 includes antioxidant properties and thereby the ability to neutralize damaging reactive oxygen species (ROS). Administration of hydrogen as a medical gas is limited by the poor water solubility and by the flammability of H2 in air. Therefore, nanocarriers have been investigated for safer and more efficient administration of hydrogen. Silicon particles are suggested for oral administration with the ability to undergo a redox reaction with water to produce H2 in vivo. The purpose of this work was to investigate the hydrogen generating abilities of silicon particles synthesized by centrifugal chemical vapor deposition (cCVD). High hydrogen generation rates up to 1310 ml/g at physiological pH 7.4 (82 % yield) were observed. An in vitro model of oral administration showed that pretreatment in artificial gastric juice did not affect hydrogen generation. Thus, the cCVD silicon particles seem to be suitable for in vivo hydrogen generation. A surface carbon coating or addition of surfactants or albumin hindered hydrogen generation. The addition of egg white reduced hydrogen generation but did not block it.

The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the drug. One mechanism that still lacks a proper interpretation is the kinetics of drug release from nanocarriers. In this work, we investigate two different types of classical enabling formulations - i) cyclodextrin solutions and ii) liposomal dispersions - by a combination of an experimental method (i.e. UV-Vis localized spectroscopy) and mathematical modelling/numerical data fitting. With this approach, we are able to discriminate precisely between the amount of drug bound to nanocarriers or freely dissolved at any time point; in addition, we can precisely estimate the binding and diffusivity constants of all chemical species (free drug/bound drug). The results obtained should serve as the first milestone for the further development of reliable in vitro/in silico models for the prediction of in vivo drug bioavailability when enabling formulations are used.

The purpose of this study was to prepare stable polymer-liposome complexes using a new, improved one-pot method. Complexes prepared by the conventional method were used as reference. The one-pot method combines the vesicle formation and complexation with the polymer in a single step allowing for fewer steps compared to the conventional thin-film method followed by coating. This has the possibility of complexing the polymer on the surface and within the aqueous core of the liposomes. Soya phosphatidylcholine (SoyPC) in combination with different amounts of either dioleoyl trimethylammoniumpropane (DOTAP, positively charged) or egg phosphatidylglycerol (Egg PG, negatively charged) were complexed with alginate or chitosan, respectively. All the alginate-liposome complexes were larger compared to the naked liposomes and the zeta potential changed from positive to negative after complexation with the polymer. Polydispersity index (PDI) analysis showed narrow size distributions implying homogenous populations. The best stability was obtained by employing 20 mol% DOTAP in the membrane. This formulation was stable during the whole four months period when the stability test was performed. The chitosan-liposome complexes were generally difficult to extrude and were larger than the alginate-liposome complexes due to the need for a larger pore size in the membrane during extrusion. Based on these results, the one-pot method can be used for preparing stable alginate-liposome complexes. For the chitosan-liposome complexes alternative methods for size reduction should be investigated.

The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (Rapp) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent - glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF's permeation, whilst HC permeability is a partition-driven process.

The effect of polymer concentration on the temperature-induced self-association of a block copolymer comprising a poly(2-ethyl-2-oxazoline) block and a random copolymer block consisting of 2-ethyl-2-oxazoline and 2-n-propyl-2-oxazoline (PEtO80-block-P(EtOxx-stat-PropO40-x) with x = 0, 4, or 8 were investigated by dynamic light scattering (DLS) and transmittance measurements (turbidimetry). The polymers reveal a complex aggregation behavior with up to three relaxation modes in the DLS data and with a transmittance that first goes through a minimum before it declines at high temperatures. At low temperatures, unassociated polymer chains were found to co-exist with larger aggregates. As the temperature is increased, enhanced association and contraction of the aggregates results in a drop of the transmittance values. The aggregates fragment into smaller micellar-like clusters when the temperature is raised further, causing the samples to become optically clear again. At high temperatures, the polymers aggregate into large compact clusters, and the samples become turbid. Interestingly, very large aggregates were observed at low temperatures when the polymer concentrations were low. The formation of these aggregates was also promoted by a more hydrophilic copolymer structure. The formation of large aggregates with an open structure at conditions where the solvent conditions are improved is probably caused by depletion flocculation of the smaller aggregates.

Positively charged liposomes were coated with the negatively charged and temperature sensitive poly(N-isopropylacrylamide-co-methacrylic acid) by electrostatic deposition. Too low or too high polymer concentrations lead to unstable suspensions. However, intermediate polymer concentrations (0.05–0.2 wt.%) result in relatively stable suspensions of polymer-coated liposomes. At elevated temperatures the thickness of the polymer layer around the coated liposomes increased sharply at 40 °C, due to the formation of polymer multilayers. At higher temperatures, a contraction of the adsorbed polymer layer was observed. The uncoated liposomes exhibited an interesting transition in size and intensity of the scattered light when heated, attributed to the transition from the gel to liquid crystalline phase. Rheo-SALS (small angle light scattering under shear conditions) measurements demonstrated that the polymer coating was stable under shear at physiological temperature. It also revealed an anomalous high scattered intensity of the uncoated liposomes compared to the coated liposomes. This discrepancy was diminished at higher temperatures, and can probably be attributed to the change from a non-spherical, polyhedron-like conformation of the uncoated liposomes in the gel phase to a spherical shape above the phase transition.

The thermal and rheological properties of suspensions of microencapsulated phase change materials (MPCM) in glycerol were investigated. When the microcapsule concentration is raised, the heat storage capacity of the suspensions becomes higher and a slight decline in the thermal conductivity of the suspensions is observed. The temperature-dependent shear-thinning behaviour of the suspensions was found to be strongly affected by non-encapsulated phase change materials (PCM). Accordingly, the rheological properties of the MPCM suspensions could be described by the Cross model below the PCM melting point while a power law model best described the data above the PCM melting point. The MPCM suspensions are interesting for energy storage and heat transfer applications. However, the non-encapsulated PCM contributes to the agglomeration of the microcapsules, which can lead to higher pumping consumption and clogging of piping systems.

Polysaccharide-based nanoparticles can be formed, under the right conditions, when a counterion is added to a dilute polysaccharide solution. In this study, the possibility of preparing stable alginate nanoparticles cross-linked with zinc was investigated. The effects of the ionic strength of the solvent and the concentration of zinc were studied. The nanoparticles were characterized by dynamic light scattering, zeta potential and pH measurements. The results showed that an increase in the ionic strength of the solvent provided nanoparticles with considerably narrower size distributions compared to pure water, and a small size. The zinc content was shown to be an important factor for the formation of the nanoparticles. In fact, a critical zinc concentration was needed to obtain nanoparticles, and below this concentration particles were not formed. A stepwise increase in the amount of zinc revealed the process of formation of the nanoparticles. The stages of the nanoparticle formation process were identified, and differences according to the ionic strength of the solvent were also reported. Furthermore, the stability test of the most promising formulation showed a stability of over ten weeks.

The aim of this work was to prepare and test different pharmaceutical formulations in respect of their potential in relieving dry mouth symptom. Since many of the products available on the market provide only temporary relief to the patients, there is need for new formulations able to retain on the oral mucosa. The prolonged moisture protection could be achieved by combining mucoadhesive materials, such as polymers containing hydrogen bonding groups, with vesicles capable of releasing hydration medium from the inner compartment. In this study three different types of liposomes (positively, negatively and neutrally charged) were coated with five different types of polymers: low-methoxylated pectin (LM-pectin), high-methoxylated pectin (HM-pectin), alginate, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose (HM-EHEC). The particle size and the zeta potential of the obtained carriers were tested by measuring dynamic light scattering (DLS) and electrophoretic mobility. Later on, selected positively charged liposomes were deposited on a negatively charged mica surface and depicted by atomic force microscopy (AFM). The water sorption properties of polymers, uncoated liposomes and polymer-coated liposomes were studied by the means of dynamic vapor sorption (DVS). The experiments were performed within the relative humidity range RH = 95–0–95%, at 35 °C. It was found that coating the liposomes with polymers significantly increased the water sorption capacity of the formulations, making them an attractive choice for hydration of the oral mucosa.

Liposomes coated with polymers may have a great potential in drug delivery. In this study, adsorption of the non-ionic hydroxyethyl cellulose (HEC) onto non-charged phospholipid vesicles was investigated. Both unmodified and hydrophobically modified (HM) HEC were included in the study. Possible interactions between the liposomes and the polymers were determined by changes in the size and the size distribution. Rheo-SALS measurements were carried out to verify the successfulness of the coating process. The stability was investigated by zeta potential measurements, UV-analysis and HPTLC. Mixing unmodified HEC (Mw 90,000 and 300,000) with the liposomes yielded no increase in the particle size. HM-HEC, however, was adsorbed onto both the fluid phase egg-PC liposomes and the gel phase DPPC liposomes. The Rheo-SALS measurements confirmed the successful coating of the liposomes. Complete coating resulted in increased chemical stability of the dispersion and in addition prevented aggregation. This study has shown that the non-ionic HM-HEC can be used to form polymer coated liposomes with neutral surface charge for enhanced stability.

The interactions between pectin coated liposomes and parotid saliva and dental enamel were studied to investigate their potential to mimic the protective biofilm formed naturally on tooth surfaces. Different pectin coated liposomes with respect to pectin type (LM-, HM- and AM-pectin) and concentration (0.05% and 0.2%) were prepared. Interactions between the pectin coated liposomes and parotid saliva were studied by turbidimetry and imaging by atomic force microscopy. The liposomes were adsorbed to hydroxyapatite (HA) and human dental enamel using phosphate buffer and parotid saliva as adsorption media. A continuous flow was imposed on the enamel surfaces for various time intervals to examine their retention on the dental enamel. The results were compared to uncoated, charged liposomes. No aggregation tendencies for the pectin coated liposomes and parotid saliva were revealed. This makes them promising as drug delivery systems to be used in the oral cavity. In phosphate buffer the adsorption to HA of pectin coated liposomes was significantly lower than the negative liposomes. The difference diminished in parotid saliva. Positive liposomes adsorbed better to the dental enamel than the pectin coated liposomes. However, when subjected to flow for 1h, no significant differences in the retention levels on the enamel were found between the formulations. For all formulations, more than 40% of the liposomes still remained on the enamel surfaces. At time point 20 min the retention of HM-pectin coated and positive liposomes were significantly higher. It was concluded that pectin coated liposomes can adsorb to HA as well as to the dental enamel. Their ability to retain on the enamel surfaces promotes the concept of using them as protective structures for the teeth.

Pectin is a polymer with well-known mucoadhesive properties. In this study, liposomes were coated with three different types of pectin. Their properties were characterized and their mucoadhesiveness was estimated by a novel in vitro approach. Two different types of commercially available mucin were investigated in order to choose the best candidate for the method. The effect of pH on the properties of the coated liposomes and the interaction with mucin was also studied. The pectin-coated liposomes and the complexes they formed with mucin were characterized by dynamic light scattering (DLS), zeta potential and turbidity measurements. The zeta potential of the liposomes shifted from positive to negative after coating with pectin. They also exhibited larger diameters, and the liposomes coated with HM-pectin were the largest. After the addition of mucin, the zeta potential shifted to a less negative value and the sizes of the pectin-coated liposomes increased. The complexes formed between mucin and the HM-pectin-coated liposomes were the largest, while the smallest were formed with the LM-pectin-coated liposomes. The pH was found to affect the interaction between the coated liposomes and mucin. DLS was conducted on an ALV goniometer to gain information about the diffusivity of the samples, the relative scattered intensities and to obtain an optimal characterization of the size distributions. The results correlated well with measurements from an automatized light scattering instrument (Zetasizer Nano ZS).

Liposomes coated with a biopolymer such as pectin have a great potential in drug delivery. The drug formulation may be less toxic and in addition the mucoadhesive properties may be increased. The aim of this study was to investigate how different important factors affect the ability to produce single stable pectin coated liposomes. Experimental design and multivariate analysis were used in order to investigate many factors in a systematic manner by the use of a minimum of experiments. In a reduced factorial design, 24–1 design, the pectin concentration, lipid concentration, amount of charged lipid and the speed of addition under preparation were investigated. A central composite design investigated the three most important factors from the 24–1 design on three levels. The response variables in the studies, analysed by multivariate analysis, were the zeta potential and the change in particle size. These two parameters are important factors for verifying a successful coating of the liposomes. Summarizing the results from both designs revealed the most important factors for a successful coating, indicated by a high negative zeta potential, to be a high amount of charge in the lipid membrane and a low lipid to pectin ratio. The size of the coated liposomes was increased when the pectin concentration was high, indicating more complete covering of the liposomes. The size increased even more with a high lipid to pectin ratio probably due to bridging flocculation. To produce stable single pectin coated liposomes it is important to have enough pectin to cover the liposomes completely. In addition the charge density of the liposomes should be high since this promotes adsorption of pectin

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 2 mol%) 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 1 mol% of hydrophobic groups, while 2 mol% 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 (1 mol% HM).

The efficacy of treatments of oral ailments is often challenged by a low residence time of the conventional pharmaceutical formulations in the oral cavity, which could be improved by using bioadhesive formulations. This in vitro study investigated charged liposomes, both uncoated and coated through electrostatic deposition with polysaccharides (chitosan, alginate and pectin), as bioadhesive systems for the oral cavity. First, formulations that provided liposomes fully coated with polysaccharide were selected. Thereafter, the stability of both the uncoated and the polysaccharide-coated liposomes was investigated in artificial saliva simulating pH, ionic strength, and ionic content of natural saliva. Additionally, adsorption to hydroxyapatite (model for tooth enamel) was tested. The surface charge was of high importance for both the stability in salivary environment and bioadhesion. In artificial saliva, the negatively charged liposomes were the most stable, and the stability of the positively charged liposomes was improved through coating with a negatively charged polysaccharide. On the contrary, the positively charged liposomes were the most bioadhesive, although a moderate adsorption was recorded for the negatively charged liposomes. Based on the present results, the negatively charged liposomes seem to be the most promising formulations used as a tooth adhesive nanosystem and could as such provide improved treatment of tooth ailments.

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33–113 ppm, and the entrapment efficiency 3.6–6.2% for chitosan nanoparticles prepared in 0.2–0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH 5 and 7 until it reached a maximum at time point 4 h and maintained at this level for at least 24 h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH 5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development.

The present review is aimed at elucidating relatively new aspects of mucoadhesion/mucus interaction and related phenomena that emerged from a Mucoadhesion workshop held in Munster on 2–3 September 2015 as a satellite event of the ICCC 13th—EUCHIS 12th. After a brief outline of the new issues, the focus is on mucus description, purification, and mucus/mucin characterization, all steps that are pivotal to the understanding of mucus related phenomena and the choice of the correct mucosal model for in vitro and ex vivo experiments, alternative bio/mucomimetic materials are also presented. Then a selection of preparative techniques and testing methods are described (at molecular as well as micro and macroscale) that may support the pharmaceutical development of mucus interactive systems and assist formulators in the scale-up and industrialization steps. Recent applications of mucoadhesive systems (including medical devices) intended for different routes of administration (oral, gastrointestinal, vaginal, nasal, ocular, and intravesical) and for the treatment of difficult to treat pathologies or the alleviation of symptoms are described.

The efficacy of treatments for oral ailments is often challenged by a low residence time of the conventional pharmaceutical formulations in the oral cavity. The residence time in the oral cavity could be improved by using bioadhesive formulations, such as preparations based on polysaccharides. This study describes the formulation and the evaluation of polysaccharide-based nanosystems as drug delivery systems addressed to the oral cavity. Nanoparticles based on chitosan, alginate or pectin were prepared through self-assembly by ionotropic gelation using oppositely charged crosslinkers (tripolyphosphate or zinc). Characteristics of nanoparticles at increasing crosslinker concentration provided the basis for selecting the most suitable formulations. The nanoparticles were tested for cytotoxicity against buccal cells (TR146) and for stability in a medium simulating pH, ionic strength, electrolyte composition and concentration of saliva. Alginate nanoparticles were the most stable in the salivary environment, while chitosan nanoparticles were the most cytocompatible. Alginate nanoparticles and pectin nanoparticles revealed possible cytotoxicity due to the presence of zinc. This knowledge is important in the early design of polymer-based nanoparticles for oral usage and for potential improving of the biocompatibility of the investigated nanoparticles with the oral environment.

Liposomes may have potentials as a drug delivery system in the oral cavity; hence, the adsorption to, oral tissues may be of importance. The aim of this study was to find an optimal liposomal formulation with appropriate in vitro stability and which liposomal formulation parameters may be of importance for the interaction to tooth enamel surfaces. Charged liposomes were adsorbed in vitro onto hydroxyapatite (HA), used as a model substance for human dental enamel. For a systematic approach of lipid selection, statistical experimental design and multivariate analysis were conducted to interpret the data. The factors investigated were the type of charge (positive, negative), type of main phospholipid (egg-PC, DPPC, DMPC), type of charged lipid (diacyl-TAP, -ethylPC, -PA, -PG, -PS), the amount of charged component (2.5, 10 mol%) and the inclusion of cholesterol in the lipid bilayer. The results indicated that positively charged liposomes expressed significantly higher adsorption levels than the negatively charged ones. The effect of incorporating cholesterol did not turn out to be significant. Both positive egg-PC and DPPC liposomes exhibited high adsorption levels; however egg-PC liposomes were unstable during storage. For positively charged liposomes, the factor “type of main lipid” was found to be of significance for the adsorption, whereas, for negatively charged liposomes, no such important factors were found. Based on the adsorption profile to HA and the in vitro stability in phosphate buffer, the most promising liposomal formulation to target for human enamel in this study was the positively charged DPPC liposomes with 10 mol% charged lipid included. However, more experiments are needed to determine the optimum mol% of positively charged lipid for the adsorption onto HA.

Polysaccharide-based nanoparticles are promising carriers for drug delivery applications. The particle size influences the biodistribution of the nanoparticles; hence size distributions and polydispersity index (PDI) are critical characteristics. However, the preparation of stable particles with a low PDI is a challenging task and is usually based on empirical trials. In this study, we report the use of multivariate evaluation to optimize the formulation factors for the preparation of alginate-zinc nanoparticles by ionotropic gelation. The PDI was selected as the response variable. Particle size, size distributions, zeta potential and pH of the samples were also recorded. Two full factorial (mixed-level) designs were analyzed by partial least squares regression (PLS). In the first design, the influence of the polysaccharide and the crosslinker concentrations were studied. The results revealed that size distributions with a low PDI were obtained by using a low polysaccharide concentrations (0.03-0.05%) and a zinc concentration of 0.03% (w/w). However, a high polysaccharide concentration can be advantageous for drug delivery systems. Therefore, in the second design, a high alginate concentration was used (0.09%) and a reduction in the PDI was obtained by simultaneously increasing the ionic strength of the solvent and the zinc concentration. The multivariate analysis also revealed the interaction between the factors in terms of their effects on the PDI; hence, compared to traditional univariate analyses, the multivariate analysis allowed us to obtain a more complete understanding of the effects of the factors scrutinized. In addition, the results are considered useful in order to avoid extensive empirical tests for future formulation studies.

Pharmaceutical formulations intended for treatment of xerostomia (dry mouth) should be able to keep the oral mucosa hydrated for a prolonged period of time. The products already existing on the market contain water-soluble polymers, however their ability to moisturize the oral mucosa for a longer period of time seems limited. In this paper the sorption properties of water vapor of high-methoxylated pectin (HM-pectin, a hydrophilic biopolymer) and phosphatidylcholine-based (Soya-PC) liposomes have been studied and compared using a gravimetric method. The kinetics of water desorption and sorption have been recorded over the relative humidity range RH = 95–0–95%, at 35 °C. The obtained isotherms were found to be well described by the n-layer Brunauer-Emmet-Teller (BET) adsorption model. The water isotherms on HM-pectin were Type II (IUPAC), while water isotherms on liposomes were Type III. The maximum water sorption capacity of liposomes (1.2 mg water per mg of adsorbent at 95% RH) was found to be twice as high as for pectin. Due to the slower water release from the liposomes, as well as their high water sorption capacity, they seem to have great potential in relieving the symptoms of dry mouth syndrome.

Drug delivery to the oral cavity poses a significant challenge due to the short residence time of the formulations at the site of action. From this point of view, nanoparticulate drug delivery systems with ability to adhere to the oral mucosa are advantageous as they could increase the effectiveness of the therapy. Positively, negatively and neutrally charged liposomes were coated with four different types of polymers: alginate, low-ester pectin, chitosan and hydrophobically modified ethyl hydroxyethyl cellulose. The mucoadhesion was studied using a novel in vitro method allowing the liposomes to interact with a mucus-producing confluent HT29-MTX cell-line without applying any external force. MTT viability and paracellular permeability tests were conducted on the same cell-line. The alginate-coated liposomes achieved a high specific (genuine) mucin interaction, with a low potential of cell-irritation. The positively charged uncoated liposomes achieved the highest initial mucoadhesion, but also displayed a higher probability of cell-irritation. The chitosan-coated liposomes displayed the highest potential for long lasting mucoadhesion, but with the drawback of a higher general adhesion (tack) and a higher potential for irritating the cells.

The in vitro adsorption and retention of liposomes onto four common types of dental restorative materials (conventional and silorane-based resin composites as well as conventional and resin-modified glass ionomer cements (GIC)) have been investigated due to their potential use in the oral cavity. Uncoated liposomes (positively and negatively charged) and pectin (low- and high-methoxylated) coated liposomes were prepared and characterized in terms of particle size and zeta potential. The adsorption of liposomes was performed by immersion, quantified by fluorescence detection, and visualized by fluorescence imaging and atomic force microscopy. Positive liposomes demonstrated the highest adsorption on all four types of materials likely due to their attractive surface charge. They also retained well (minimum 40% after 60 min) on both conventional resin composite and GIC even when exposed to simulated salivary flow. Although an intermediate initial level of adsorption was found for the pectin coated liposomes, at least 70% high methoxylated-pectin coated liposomes still remained on the conventional resin composite after 60 min flow exposure. This indicates significant contribution of hydrophobic interactions in the prolonged binding of liposomes to resin composites. Based on these results, the present paper suggests two new possible applications of liposomes in the preservation of dental restorations.

In this study phase separation, structure, and dynamics of aqueous pectin-chitosan mixtures of different ratios and a pure aqueous pectin sample have been investigated under various conditions by turbidimetry, SANS and dynamic light scattering (DLS). Only the mixture with r = 0.75 gelled upon decreasing the temperature ((rmpectin/(mpectin + mchitosan), where m denotes the mass of the considered component). The pure pectin sample (r = 1) did not gel and the decrease in temperature seemed to promote phase separation. The addition of chitosan reduced the tendency of pec- tin to phase separate in the mixtures of pectin and chitosan. The general trend when cooling the samples was that the turbidity and the growth of the turbidity became more pronounced as the amount of pectin in the mixture was increased. The wavelength dependence of the turbidity indicated a change of the conformation of pectin chains from an extended form to a more compact structure in pectin solutions without chitosan as the temperature decreased. This was not observed for the mixture of pectin and chitosan. SANS measurements revealed excess scattered intensity in the low wave vector area with the strongest upturn for the pure pectin sample (r = 1). DLS experiments showed longer slow relaxation times after a temperature quench for all samples, with the most pronounced effect for the mixture of pectin and chitosan with r = 0.75. The synergism between pectin and chitosan at high pectin contents (r = 0.75) generated large association complexes over time. � 2005 Elsevier Ltd. All rights reserved.

Effects of oscillatory and steady shear flows on intermolecular associations in dilute and semidilute aqueous solutions of pectin in the absence and presence of the hydrogen bond breaking agent urea are reported. A weak oscillatory shear perturbation builds up, depending on polymer concentration, multichain aggregates or networks in the course of time and these association structures are mainly stabilized through hydrogen bonds. The association effect is more pronounced at higher concentrations, and the growth of intermolecular interactions is inhibited by the addition of urea. Steady shear measurements on the pectin–water solutions reveal shear thickening at low shear rates for all the concentrations, except the lowest one, and disruption of intermolecular junctions at high shear rates. In the presence of urea, no shear thickening is detected. The polymer concentration dependence of the viscosity at a low shear rate can be described by a power law η ∼ cx, with x = 1.9 and 1.4 without and with urea, respectively. When a low constant shear rate is applied to pectin solutions and this monitoring shear rate is interrupted periodically by transitory high shear rates perturbations during a short time, prominent association structures evolve upon return to the monitoring shear rate. This effect is more evident at a lower polymer concentration, and in the presence of urea, the growth of the association complexes is damped. The shear-induced alignment and stretching of polymer chains and the formation of hydrogen-bonded structures are analyzed in the framework of a model, where cooperative zipping of stretched chains play an important role. Viscosity enhancement is found for a semidilute pectin–water solution in the presence of moderate levels of salt addition (NaCl), suggesting that partial screening of electrostatic interactions promotes growth of energetic cross-links.

Dynamic light scattering (DLS) measurements were carried out on aqueous solutions of low-methoxyl pectin at different temperatures and polymer concentration. Low temperature and increased polymer concentration promote the formation of multichain aggregates. The time correlation data obtained from the DLS experiments revealed, for all polymer solutions, the existence of two relaxation modes, one single exponential at short times followed by a stretched exponential at longer times. In the semidilute regime, a temperature reduction induced enhanced chain associations in the solutions with high values of the slow relaxation time and a strong wave vector dependence of the slow mode. These features could be rationalized in the framework of the coupling model of Ngai. At low temperatures (10 °C), gelation occurs in the semidilute regime and a transparent gel is formed. In this state, the profile of the correlation function changes and nonergodic signs are observed. The conjecture is that the association complexes and the gel network are stabilized through intermolecular hydrogen bonds, which are broken-up at higher temperatures. The hydrogen-bonded structures are formed in a process where the polymer chains have been “zipped” together in a cooperative manner.

The present study investigated the surface coating of charged liposomes by three different types of pectin (LM, HM and amidated pectin) by particle size determinations and zeta potential measurements. The pectins and the pectin coated liposomes were visualized by atomic force microscopy. The adsorption of pectin onto positive liposomes yielded a reproducible increase in particle size and a shift of the zeta potential from positive to negative side for all three pectin types, whereas the adsorption of pectin onto negative liposomes did not render any significant changes probably due to electrostatic repulsion. The positive liposomes coated with HM-pectin gave the largest pectin coated particles with the least negative zeta potential, while the opposite was observed for the LM-pectin coated positive liposomes. Furthermore, results from dynamic light scattering revealed narrow size distributions, indicating that the degree of aggregation was low for the pectin coated liposomes. As liposomes are able to encapsulate drugs and pectin has been found to be mucoadhesive, these pectin coated liposomes may be potential drug delivery systems.