RESUMEN
The introduction of fish vaccination has had a tremendous impact on the aquaculture industry by providing an important measurement in regard to disease control. Infectious diseases caused by intracellular pathogens do, however, remain an unsolved problem for the industry. This is in many cases directly connected to the inability of vaccines to evoke a cellular immunity needed for long-term protection. Thus, there is a need for new and improved vaccines and adjuvants able to induce a strong humoral and cellular immune response. We have previously shown that membrane vesicles (MVs) from the intracellular fish pathogen Piscirickettsia salmonis are able to induce a protective response in adult zebrafish, but the incorporation of an adjuvant has not been evaluated. In this study, we report the use of chitosan as an adjuvant in combination with the P. salmonis-derived MVs for improved immunization against P. salmonis. Both free chitosan and chitosan-coated MVs (cMVs) were injected into adult zebrafish and their efficacy evaluated. The cMVs provided a significant protection (p < 0.05), while a small but nonsignificant reduction in mortalities was registered for fish injected with free chitosan. Both free chitosan and the cMVs were shown to induce an increased immune gene expression of CD 4, CD 8, MHC I, Mpeg1.1, TNFα, IL-1ß, IL-10, and IL-6, but to a higher degree in the cMV group. Taken together, the results indicate a potential use of chitosan-coated MVs for vaccination, and that zebrafish is a promising model for aquaculture-relevant studies.
Asunto(s)
Vacunas Bacterianas/administración & dosificación , Quitosano/administración & dosificación , Vesículas Citoplasmáticas/química , Enfermedades de los Peces/prevención & control , Infecciones por Piscirickettsiaceae/prevención & control , Sepsis/prevención & control , Pez Cebra , Adyuvantes Inmunológicos , Animales , Quitosano/química , Modelos Animales de Enfermedad , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Innata , Inmunización , Piscirickettsia/inmunología , Infecciones por Piscirickettsiaceae/inmunología , Infecciones por Piscirickettsiaceae/microbiología , Sepsis/inmunología , Sepsis/microbiologíaRESUMEN
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.
Asunto(s)
Quitosano/química , Liposomas/química , Boca/metabolismo , Mucinas/química , Pectinas/química , Línea Celular , Supervivencia Celular , Celulosa/análogos & derivados , Celulosa/química , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Liposomas/farmacología , Nanopartículas/química , Tamaño de la Partícula , Permeabilidad , Propiedades de SuperficieRESUMEN
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).
Asunto(s)
Celulosa/análogos & derivados , Liposomas , Celulosa/química , Colorantes Fluorescentes/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
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.
Asunto(s)
Portadores de Fármacos/química , Liposomas/química , Xerostomía/tratamiento farmacológico , Alginatos , Celulosa/análogos & derivados , Química Farmacéutica , Quitosano , Composición de Medicamentos , Ácido Glucurónico , Ácidos Hexurónicos , Humanos , Tamaño de la Partícula , Pectinas , PolímerosRESUMEN
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 33-113ppm, 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 pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. 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.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas/química , Fluoruro de Sodio/química , Alginatos/química , Quitosano/química , Liberación de Fármacos , Estabilidad de Medicamentos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Pectinas/químicaRESUMEN
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.
Asunto(s)
Mucosa Bucal/efectos de los fármacos , Nanopartículas/administración & dosificación , Nanopartículas/química , Polisacáridos/administración & dosificación , Polisacáridos/química , Administración Oral , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Química Farmacéutica , Humanos , Mucosa Bucal/metabolismoRESUMEN
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.
Asunto(s)
Alginatos/química , Quitosano/química , Sistemas de Liberación de Medicamentos , Pectinas/química , Adhesividad , Adsorción , Química Farmacéutica/métodos , Portadores de Fármacos/química , Durapatita/metabolismo , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Liposomas , Boca , Nanoestructuras , Concentración Osmolar , Polisacáridos/química , Saliva/metabolismo , Electricidad EstáticaRESUMEN
In this study the development of stable polyelectrolyte-surfactant complex nanoparticles composed of alginate and cetylpyridinium chloride (CPC), with and without ZnCl2, for therapeutic use, is investigated. The mechanism of CPC binding by alginate was analyzed using a cetylpyridinium cation (CP(+)) selective membrane electrode. The cooperative nature of the interaction between CP(+) and alginate was underlined by the sigmoidal shape of the binding isotherms. The presence of salts was shown to weaken interactions and, moreover, ZnCl2 reduced the cooperativity of binding. The CP(+) cations in the form of micellar associates acted as multivalent crosslinkers of the alginate chains where stable dispersions of CP-alginate nanoparticles were formed in water at CP(+)/alginate charge ratios from 0.2 to 0.8. Characterization of the nanoparticles showed hydrodynamic diameters from 140 to 200nm, a polydispersity index below 0.2, a negative zeta potential and spherical morphology. The entrapment efficiency of CPC was â¼94%, the loading capacity more than 50% and prolonged release over 7days were shown. The formulations with noted charge ratios resulted in stable CP-alginate nanoparticles with a potential of treating periodontal disease.
Asunto(s)
Alginatos/química , Cetilpiridinio/farmacocinética , Nanopartículas/química , Cetilpiridinio/química , Cloruros/química , Liberación de Fármacos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Micelas , Tamaño de la Partícula , Compuestos de Zinc/químicaRESUMEN
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.
Asunto(s)
Portadores de Fármacos/química , Análisis Multivariante , Nanopartículas/química , Polisacáridos/química , Concentración de Iones de Hidrógeno , Concentración OsmolarRESUMEN
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 (1.2mg 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.
Asunto(s)
Pectinas/química , Fosfatidilcolinas/química , Polímeros/química , Agua/química , Adsorción , Química Farmacéutica/métodos , Humedad , Cinética , Liposomas , Solubilidad , Factores de Tiempo , Xerostomía/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Adhesivos/química , Liposomas/química , Liposomas/metabolismo , Moco/metabolismo , Polímeros/química , Polímeros/metabolismo , Membrana Celular/metabolismo , Supervivencia Celular/fisiología , Células Cultivadas , Células HT29 , HumanosRESUMEN
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.
Asunto(s)
Materiales Dentales , Restauración Dental Permanente , Liposomas , Adsorción , Microscopía de Fuerza AtómicaRESUMEN
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.
Asunto(s)
Alginatos/química , Nanopartículas del Metal/química , Zinc/química , Alginatos/síntesis química , Ácido Glucurónico/síntesis química , Ácido Glucurónico/química , Ácidos Hexurónicos/síntesis química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Concentración Osmolar , Cloruro de Sodio/químicaRESUMEN
UNLABELLED: Commercially available parenteral emulsions (n = 4) and admixtures for parenteral nutrition (n = 2) were exposed to UVA and visible irradiation (320-800 nm) at standardized, validated conditions according to the ICH Guideline Q1B (Option 1, to an endpoint corresponding to 1.2 × 10(6) lux h in the range 400-800 nm). Physical stability was evaluated as changes in emulsion droplet size measured by photon correlation spectroscopy, and emulsion droplet zeta potential measured by micro-electrophoresis. Chemical stability was evaluated by detection of lipid peroxidation according to the thiobarbituric acid test and changes in pH. The results are valid for samples stored up to 24 h after exposure. The preparations remained physically stable, even though exposed to UVA (489 W h/m(2)) and visible radiation (1.2 × 10(6) lux h) that correspond to as much as 2-4 days exposure on a sunny window sill. This was the case also when vitamins and trace metals were added. Spiking of the samples with the highly efficient photosensitizer 5-hydroxymethyl furfural (5-HMF), a thermal degradation product of glucose commonly present in steam-sterilized glucose infusions, did not reduce physical stability. Hence, the lipid peroxidation and changes in pH and color induced by irradiation of certain preparations did obviously not influence their physical stability. LAY ABSTRACT: Parenteral preparations are commonly exposed to optical radiation during storage and administration. Exposure to visible light and UVA radiation indoors, or additionally UVB radiation outdoors, may lead to degradation of active pharmaceutical ingredients and drug formulations. Clear plastic and glass containers commonly used for parenteral preparations do not protect the contents from exposure to radiation, even in the UVB region. The investigated parenteral emulsions and admixtures of emulsions, glucose, and amino acids are physically stable during exposure to optical radiation corresponding to indoor conditions (i.e., glass-filtered daylight). They can be considered physically stable under normal in-use conditions.
Asunto(s)
Embalaje de Medicamentos , Soluciones para Nutrición Parenteral/química , Preparaciones Farmacéuticas/química , Fotólisis , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Emulsiones , Vidrio , Concentración de Iones de Hidrógeno , Peroxidación de Lípido , Plásticos , Rayos UltravioletaRESUMEN
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.
Asunto(s)
Acrilamidas/química , Calor , Liposomas/química , Ácidos Polimetacrílicos/químicaRESUMEN
The influence of four Pluronics block copolymers (i.e. F68, P123, F127, and L44) on the aggregation and solubilization of five structurally related meso-tetraphenyl porphyrin photosensitizers (PS) as model compounds for use in Photodynamic Therapy of cancer (PDT) was evaluated. Interactions between the PSs and Pluronics were studied at micromolar concentration by means of UV-Vis absorption spectrometry and by kinematic viscosity (υ) and osmolarity measurements at millimolar concentrations. Pluronic micelles were characterized by size and zeta potential (ζ) measurements. The morphology of selected PS-Pluronic assemblies was studied by atomic force microscopy (AFM). While hydrophobic 5,10,15,20-Tetrakis(4-hydroxyphenyl) porphine (THPP) seemed to be solubilized in the Pluronic micellar cores, amphiphilic di(monoethanolammonium) meso-tetraphenyl porphine disulphonate (TPPS2a) was likely bound to the micellar palisade layer. Hydrophilic PSs like 5,10,15,20-Tetrakis (4-trimethylaniliniumphenyl) porphine (TAPP) seemed to form complexes with Pluronic unimers and to be distributed among the micellar coronas. TPPS2a aggregated into a network which could be broken at Pluronic concentration [Formula: see text] cmc, but would reconstitute in the presence of tonicity adjusting agents, e.g. sodium chloride (NaCl) or glucose.
Asunto(s)
Mesoporfirinas/química , Fármacos Fotosensibilizantes/química , Poloxámero/química , Tensoactivos/química , Interacciones Hidrofóbicas e Hidrofílicas , Mesoporfirinas/metabolismo , Microscopía de Fuerza Atómica/métodos , Tamaño de la Partícula , Fármacos Fotosensibilizantes/metabolismo , Poloxámero/metabolismo , Solubilidad , Tensoactivos/metabolismoRESUMEN
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.
Asunto(s)
Celulosa/análogos & derivados , Materiales Biocompatibles Revestidos/química , Liposomas/química , Fosfolípidos/química , Polímeros/química , 1,2-Dipalmitoilfosfatidilcolina/química , Animales , Celulosa/química , Hidrodinámica , Interacciones Hidrofóbicas e Hidrofílicas , Iones , Luz , Tamaño de la Partícula , Dispersión del Ángulo Pequeño , Electricidad Estática , Propiedades de SuperficieRESUMEN
Nanoparticles were prepared by ionotropic gelation of low-methoxylated (LM) and amidated low-methoxylated (AM) pectin with zinc chloride (ZnCl2) in aqueous media. The samples were characterized by atomic force microscopy, dynamic light scattering, turbidimetry, zeta potential, and pH measurements. Pectin nanoparticles could be prepared at a pectin concentration of 0.07% (w/w) and a ZnCl2-to-pectin ratio of 15:85 (w/w) in the presence of sodium chloride, but not in pure water. Interestingly, particles in the nanometer size-range could also be prepared in the absence of the cross-linker ZnCl2. The dynamic light scattering studies revealed that the AM-pectin nanoparticles were much less polydisperse than the LM-pectin nanoparticles. The AM-pectin nanoparticles were therefore considered to be more promising as a potential drug delivery system, and further studies were performed to investigate the colloidal stability and the effect of the pectin concentration on the size, charge, and compactness of these nanoparticles.
Asunto(s)
Cloruros/química , Reactivos de Enlaces Cruzados/síntesis química , Nanopartículas/química , Pectinas/síntesis química , Sodio/química , Zinc/química , Cationes/química , Reactivos de Enlaces Cruzados/química , Concentración de Iones de Hidrógeno , Iones/síntesis química , Iones/química , Tamaño de la Partícula , Pectinas/química , Propiedades de SuperficieRESUMEN
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).
Asunto(s)
Liposomas/metabolismo , Mucinas/metabolismo , Pectinas/metabolismo , Animales , Hidrodinámica , Concentración de Iones de Hidrógeno , Luz , Nefelometría y Turbidimetría , Dispersión de Radiación , Soluciones , Electricidad Estática , Sus scrofaRESUMEN
The aim of the present study was to investigate the potential of different types of pectin as stabilizers for liposomal drug delivery systems. Positively charged liposomes were coated with commercially available and purified low-methoxylated (LM), high-methoxylated (HM) and amidated (AM) pectins. The samples were stored for up to 12 weeks at 4°C, at room temperature and at 35°C. The change in liposomal size and size distribution, zeta potential, pH, leakage of encapsulated carboxyfluorescein (CF), and lipid degradation were studied. All the types of pectin were found to protect the liposomes against aggregation during storage. The pectin coat did not affect the permeability of the liposome membrane. HM and LM pectin seemed to be the most promising types of pectin due to minimal changes in the zeta potentials during storage for these samples and no detectable lipid degradation. It is concluded that pectin may be used for stabilizing liposomal drug delivery systems.