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1.
Time-programmed release of macromolecular drugs was achieved by utilization of calcium-alginate gel beads modified with coated copolymer layers. Modified calcium-alginate gel beads coated with poly(carboxy-n-propylacrylamide-co-dimethylacrylamide) [poly(CNPAAm-co-DMAAm)] (22.7 mol% of CNPAAm) of varying coating thickness from 25 to 125 μm were developed as drug carriers. Model macromolecular drugs used were fluorescein isothiocyanate (FITC)-labeled dextrans with different molecular weights ranging from 9400 to 145 000. FITC-dextran release was strongly dependent on both copolymer coating thicknesses and the dextran molecular weights. Release of FITC-dextran (MW 9400) followed Fickian diffusion according to t1/2 dependence, indicating that the drug diffusion is the main driving force for release of dextran MW 9400. Release of higher molecular weight FITC-dextrans (71 200 and 145 000) exhibited a burst-effect preceded by a preset lag time. These release profiles were governed by the dissociation of calcium ions from polyguluronate sequences in alginate molecules along with the diffusion of sodium ions into the gel bead core. This created osmotic pressure inside the gel, inducing breakage of the coated copolymer layer and accelerated drug release. Burst release of macromolecular drugs thus occurred after a certain lag period. The lag time was regulated by the copolymer coat thickness. A pulsatile release of FITC-dextran was demonstrated by combining a series of modified alginate gel beads in a single batch.  相似文献   

2.
This paper presents a mathematical model of in-mouth volatile release from gelled emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS-Breath analysis is presented to demonstrate the effect of particle size, oil content and oil-water partition coefficients. It is shown that in-mouth release of aroma from the dispersion of gelled emulsion particles follows a two-component kinetic equation with fast and slow components. Both the fast and slow rate constants depend on the particle size, oil content and oil water partition coefficient of the aroma. The relative amount of aroma contributing to the fast and slow components also depends on the size of the particles. In order to understand this unexpected behaviour, an analytical model was developed that considers the interplay between the mass transfer of flavour across the interface of the particles and that across the air-liquid interface. Analytical expressions for the two rate constants and the relative ratio of aroma contributing to the fast component have been derived. From this model, three regimes of in-mouth release of aroma from the dispersion of gelled emulsion particles were identified including, the emulsion regime, the transition regime and the gel particle regime. In the emulsion regime, changes in the size of gelled emulsion particles had negligible impact on the overall release. In the transition regime, the release was controlled by the interaction of flavour transfer from the particles with that across the air-water interface. In the gel particle regime, aroma release at long times was governed by the particles and that at short times was governed by the air-water interface, and the two processes were fully decoupled. A simple relationship was derived for the critical size above which the release of aroma from the dispersion of gelled emulsion particles is affected by the size of the particles.  相似文献   

3.
Human serum albumin (HSA) was encapsulated as a model protein in microspheres of biodegradable and biocompatible polymers by the water-in-oil-in-water (w/o/w) emulsion solvent extraction/evaporation (double emulsion) technique for purpose of controlled release. To improve the properties and control the rate of drug release of the delivery vehicle, materials with different hydrophobicity from that of their conventional counterparts, such as poly(lactide-co-ethylene glycol) (PELA) in place of poly(lactide-co-glycolide) (PLGA) as the polymer matrix, ethyl acetate/acetone in place of dichloride methane (DCM) as the (co)solvent and d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as the additive, were used to prepare the microspheres. It has been found that PELA microspheres, compared with PLGA ones, were slightly smaller in size if prepared at identical emulsification strength. They had more porous surface and internal structure, higher encapsulation efficiency (EE) and more rapid in vitro release rate. Furthermore, the physical properties of the microspheres were also affected by the presence of solvents and additives and their properties. Our results suggest that these materials could have interesting potential applications in preparation of polymeric microspheres for controlled protein release.  相似文献   

4.
A synthetic route to amphiphilic conetwork (APCN) gels was developed and involved (1) a ring-opening polymerization (ROP) synthesis of the macromonomer HEMA-PLLA/PDLA, and (2) a radical polymerization of a stereocomplex of the synthesized macromonomers with P(MEO2MA-co-OEGMA) to form the APCN gels. The structure of the gel was successfully verified using X-ray diffraction. Thermal analysis and differential scanning calorimetry data showed that the thermal behaviors of the gels were greatly improved compared with that of polylactic acid (PLA). The mechanical properties of the gels were measured by using a dynamic viscometer, and the results indicated a greater mechanical strength before swelling than afterwards, and an increasing strength of the gels with increasing amount of PLA stereocomplex. Gels placed in different aqueous phases at different temperatures showed different swelling ratio (SR) values. Specifically, the SR gradually decreased as the temperature was increased, indicating a temperature sensitivity of the gels. In addition, the gels placed in the aqueous and organic phases presented as hydrogels and hydrophobic gels, respectively, and their SR values were relatively low. These results indicated the amphiphilic nature of the gel, and indicated great application prospects for the gel in biomedicine.

A synthetic route to amphiphilic conetwork (APCN) gels was developed and involved (1) ring-opening polymerization synthesis of the macromonomer, and (2) radical polymerization of stereocomplex of the synthesized macromonomers with MEO2MA, OEGMA to form the APCN gels.  相似文献   

5.
The structure of scleroglucan gel matrices was characterized by dynamic rheological studies. The results were compared with the release kinetics of theophylline in analogous samples using a Franz diffusion cell, fitting the drug release data with a semi-empirical power law. Dynamic rheology gave information about the viscous and elastic components (loss and storage moduli, respectively) of the gel which could influence the drug-release profiles. Scleroglucan gels showed two structural transitions within the gel regime that coincided with changes in the release pattern. It was found that the introduction of 0.4% (w/w) of theophylline decreased the loss and storage moduli in the 2% (w/w) scleroglucan gels by 50%. The influence of the same wt.% theophylline in other gels was strongly dependent on the gel concentration. These results demonstrated the value of rheological studies to detect matrix structural changes produced by the inclusion of drugs which may modify the drug-release profile.  相似文献   

6.
Lactobionic acid bearing galactose group was coupled with chitosan for liver specificity, and poly(ethylene glycol) (PEG) was grafted to galactosylated chitosan (GC) for stability in water and enhanced cell permeability. Complex formation of galactosylated chitosan-graft-PEG (GCP)/DNA complexes was confirmed by agarose gel electrophoresis. Compared to GC/DNA complex, the stability of GCP/DNA complex could be enhanced. Particle sizes of GCP/DNA complexes decreased as the charge ratio of GCP to DNA increased and had a minimum value around 27 nm at the charge ratio of 5. Conformational change of DNA did not occur after complex formation with GCP compared to conformation of DNA itself. GCP/DNA complexes were only transfected into Hep G2 having asialoglycoprotein receptors (ASGR), indicative of specific interaction of ASGR on cells and galactose ligands on GCP.  相似文献   

7.
Hydrogels, physically crosslinked through stereocomplex formation, were obtained by mixing aqueous solutions of dextran with L-lactic acid grafts and dextran with D-lactic acid grafts. Protein-loaded hydrogels were simply prepared by dissolving the protein in these dextran solutions prior to mixing. It was shown that under physiological conditions the gels are fully degradable. When the gels were exposed to an aqueous buffer solution, they first showed a swelling phase in which their weight increased 2-3 times due to absorption of water, followed by a dissolution phase. The degradation time depended on the composition of the hydrogel, i.e., the number of lactate grafts, the length and polydispersity of the grafts and the initial water content, and varied from 1 to 7 days. Most likely, the degradation of the stereocomplex hydrogel started with hydrolysis of the carbonate ester, which links the lactate graft to dextran. The gels showed a release of the entrapped model proteins (IgG and lysozyme) over 6 days and the kinetics depended on the gel characteristics, such as the polydispersity of the lactate grafts and the initial water content. Lysozyme was mainly released by Fickian diffusion, indicating that its hydrodynamic diameter is smaller than the hydrogel mesh size. On the other hand the release of IgG was governed by diffusion as well as swelling/degradation of the hydrogel. Importantly, the proteins were quantitatively released from the gels and with full preservation of the enzymatic activity of lysozyme, emphasizing the protein-friendly preparation method of the protein-loaded stereocomplex hydrogel.  相似文献   

8.
This paper studies the synthesis and properties of anionic and/or amphiphilic pullulan microparticles crosslinked with epichlorohydrine or with sodium trimethaphosphate. The polysaccharide gels were physicochemically characterized and their interaction with enzymes (lysozyme) was studied with the aim to appreciate the performances for separation/purification/immobilization of the enzymes or controlled release drug systems.  相似文献   

9.
In this work, we demonstrate that liposome gels in which liposomes are connected by polyethylene glycol terminated by cholesterol groups at both ends can store hydrophilic and hydrophobic drugs in the gel interiors, inner aqueous phases, and lipid membranes. The addition of cyclodextrins (CDxs) as extrinsic stimuli led to the release of drug-entrapping liposomes due to the interactions between CDxs and cholesteryl groups and/or the alkyl chains of lipids. The addition of aqueous solutions of β-CDx, dimethyl-β-CDx, trimethyl-β-CDx, and γ-CDx (final concentration: 7.5 mM) induced the solation of liposome gels and the release of liposomes accompanying the solation. Furthermore, the addition of β-CDx led to the partial release of hydrophilic drugs encapsulated in the liposomes, although the drug release was scarcely observed in other CDxs. In particular, the addition of trimethyl-β-CDx, which has low cytotoxicity, accelerated solation, and cationic liposomes released from the gels were effectively taken up by murine colon cancer (Colon26) cells. Thus, we propose that liposomes released from liposome gels can function as drug carriers.

The solation of liposome gels owing to the addition of trimethyl-β-cyclodextrin (TMe-β-CDx) and the uptake of cationic liposomes released from liposome gels by Colon26 cells are demonstrated.  相似文献   

10.
Novel thermo-responsive inorganic-organic hybrid gels were prepared by hybridizing porous silica and poly(N-isopropylacrylamide) gels (PNIPAAm gel). The internal pores of the silica were filled with PNIPAAm gel to give a thermo-responsive drug reservoir. Brilliant blue FCF (BB) was also added to the hybrid gels for release. The BB release rate was faster above the lower critical solution temperature (LCST) of the PNIPAAm gel than below the LCST. When the temperature changed across the LCST, reversible and thermo-responsive release behavior was observed. The transition of the release behavior upon changing the temperature was similar to the behavior of the PNIPAAm gel itself. The BB release rate can be controlled simply by changing the amount of PNIPAAm gel loaded into the silica.  相似文献   

11.
In this study, controlled release gel formulations containing dihydroalprenolol (DHA), hydrocortisone (HC) or testosterone (TS) in Carbopol 934P (C934) were evaluated using pig nasal mucosa in a horizontal Ussing chamber. The controlled release gel formulations were designed by including DHA in vesicle bilayers formed with sodium dodecyl sulphate (SDS) (1.4 and 36 mM) and by partitioning TS to the core of Brij 58 (B58, 1%) micelles. For comparison, unmodified gels and solutions of the drugs and additives were examined in parallel experiments. The viability and toxicity were evaluated with electrophysiological measurements and light microscopy. The results showed that C934 did not affect the viability of the mucosa and that the rate and profile of the appearance on the receiver side was independent of whether the substances were released from an unmodified gel or an unmodified solution. Continuous electrophysiological measurements made during exposure showed that B58 (1%) and SDS (1.4 mM) inactivated the mucosa, whereas SDS (36 mM) activated it. Investigations made after a 90-min exposure to the formulations showed that all the modified gels had inactivated the mucosa and had negative effects on the morphology. For the TS-B58 (1%) and the DHA-SDS (36 mM) gels, the rate-limiting step in transport was the release from the formulation. The results confirmed that gels from C934 are suitable for nasal administration and also clearly indicated the different degrees of toxicity of the controlled release formulations evaluated in this study. The horizontal Ussing chamber method was a suitable tool for the evaluation of gels for nasal administration.  相似文献   

12.
Water-in-oil-in-water (w/o/w) emulsions containing chitosan and tryptophan in the inner aqueous phase were prepared. The acids used to dissolve chitosan were formic, acetic, butyric and lactic acids. The effects of these organic acids and pH of the inner aqueous phase on the release of tryptophan and on the separation of the aqueous phase due mainly to creaming up during storage were studied. When the inner aqueous phase was an acidic chitosan solution, the release rate was almost the same irrespective of the acids mentioned above. When acetic and butyric acids were neutralized with sodium hydroxide, the release of tryptophan was prolonged. However, it was enhanced again by an excess amount of sodium hydroxide. On the other hand, the release was enhanced after neutralization of formic and lactic acids. Separation of the aqueous phase from the w/o/w emulsion during storage was remarkably delayed after neutralizing the chitosan solution containing acetic or butyric acids, while not so much in the cases of formic and lactic acids. It is concluded that these w/o/w emulsions were stabilized in the presence of neutralized chitosan gel suspensions containing acetate or butyrate ions in the inner aqueous phase.  相似文献   

13.
This study reports that tumor-targeting glycol chitosan nanoparticles with physically loaded and chemically conjugated photosensitizers can be used in photodynamic therapy (PDT). First, the hydrophobic photosensitizer, chlorin e6 (Ce6), was physically loaded onto the hydrophobically-modified glycol chitosan nanoparticles (HGC), which were prepared by self-assembling amphiphilic glycol chitosan-5β-cholanic acid conjugates under aqueous conditions. Second, the Ce6s were chemically conjugated to the glycol chitosan polymers, resulting in amphiphilic glycol chitosan-Ce6 conjugates that formed self-assembled nanoparticles in aqueous condition. Both Ce6-loaded glycol chitosan nanoparticles (HGC-Ce6) and Ce6-conjugated chitosan nanoparticles (GC-Ce6) had similar average diameters of 300 to 350 nm, a similar in vitro singlet oxygen generation efficacy under buffer conditions, and a rapid cellular uptake profile in the cell culture system. However, compared to GC-Ce6, HGC-Ce6 showed a burst of drug release in vitro, whereby 65% of physically loaded drugs were rapidly released from the particles within 6.5 h in the buffer condition. When injected through the tail vein into tumor bearing mice, HGC-Ce6 did not accumulate efficiently in tumor tissue, reflecting the burst in the release of the physically loaded drug, while GC-Ce6 showed a prolonged circulation profile and a more efficient tumor accumulation, which resulted in high therapeutic efficacy. These comparative studies with drug-loaded and drug-conjugated nanoparticles showed that the photosensitizer-conjugated glycol chitosan nanoparticles with excellent tumor targeting properties have potential for PDT in cancer treatment.  相似文献   

14.
The aim of this study was to examine the stability of bovine serum albumin (BSA) in poly(DL-lactic acid-co-glycolic acid) (PLGA) microspheres upon addition of a new excipient, poly(ethylene glycol)-poly(L-histidine) diblock copolymer (PEG-PH). Poly(L-histidine) component can form an ionic complex with BSA under acidic conditions within a narrow pH range. To optimize the ionic complexation conditions for BSA with PEG-PH, the resulting complex sizes were monitored using the Zetasizer. PLGA microspheres containing BSA as a model protein were prepared by w/o/w double emulsion method. BSA stability in aqueous solutions and after release from PLGA microspheres was determined using circular dichroism (CD) spectroscopy for secondary structure analyses and fluorescence measurements for tertiary structure analyses. The release profile of BSA from the microspheres was monitored using UV spectrophotometry. The rate of PLGA degradation was monitored by gel permeation chromatography. The pH profile within microspheres was further evaluated by confocal microscopy using a pH-sensitive dye. Approximately 19 PEG-PH molecules and one BSA molecule coalesced to form an ionic complex around a pH range of 5.0-6.0. Plain BSA/PLGA and BSA/PEG-PH/PLGA microspheres had a mean size of 27-35 microm. PLGA microspheres with a BSA loading efficiency >80% were prepared using the double emulsion method. PEG-PH significantly improved the stability of BSA both in aqueous solutions and in PLGA microspheres. The release profiles of BSA from different formulations of PLGA microspheres were significantly different. PEG-PH effectively buffered the local acidity inside the microspheres and improved BSA release kinetics by reducing initial burst release and extending continuous release over a period of time, when encapsulated as an ionic complex. PLGA degradation rate was found to be delayed by PEG-PH. There was clear evidence that PEG-PH played multiple roles when complexed with BSA and incorporated into PLGA microspheres. PEG-PH is an effective excipient for preserving the structural stability of BSA in aqueous solution and BSA/PLGA microspheres formulation.  相似文献   

15.
Two dimensional films and paper-like structures (60–170 μm thick) have been facilely fabricated by casting ethanolic dispersions of amphiphilic and amphoteric protein microfibrils (ca. 1.3 μm width; 53 μm length) under controlled temperatures and moisture levels. Surface hydrophilicity or hydrophobicity can be easily tuned by the abillity of the highly responsive microfibers to self-organize at the interface to mimic the hydrophilicity or hydrophobicity of cast substrates. For instance, surfaces cast on hydrophobic polystyrene or Teflon were moderately hydrophobic with water contact angles (WCAs) of 54°–71° while those on hydrophilic glass or exposed to air were hydrophilic (WCAs: 5°–10°). Thin film dried in the presence of moisture (60% RH) at 65 °C had the highest crystallinity (CrI: 56%) and β structure (64%), including 48% β-sheet form, and exhibited moisture-responsive Tg, pH-responsive planar swelling, and excellent wet resiliency in extremely acidic (pH = 0) to basic (pH = 10) conditions. The pH-dependent release of highly water-soluble cationic methylene blue bound to protein microfibril (SPMF) films attests to their amphoterism and demonstrates the applicability of such 2D structures for pH-dependent controlled release of other cationic and anionic species. Such versatility of amphiphilic and amphoteric protein microfibrils can be engineered into 2D structures with tunable surface hydrophilicity and hydrophobicity, moisture- and pH-responsive behaviors and controlled release capabilities.

2D structures from amphiphilic and amphoteric protein microfibrils with tunable surface amphiphilicity, pH-responsive controlled release of cationic and anionic species.  相似文献   

16.
Ion-exchange microspheres (MS) designed as a drug delivery system for embolization coupling ability to occlude vessels and chemotherapy were used to evaluate a manufacturing process allowing to control the drug release rate through reduction of diffusion rate of the drug within the particle by impregnation of calcium alginate inside the porous MS. Impregnation was performed by diffusion of sodium alginate inside DEAE-Trisacryl(R) MS, dispersion of the MS in deionised water and gelling alginate by adding CaCl(2) to the dispersed MS. Studied parameters were alginate concentration, alginate diffusion time and calcium concentration. Indomethacin was loaded into the MS by eluting an aqueous indomethacin solution through a chromatographic column packed with impregnated MS. Indomethacin loading was reduced by alginate. Swelling studies showed indomethacin loading enhanced the hydrophobicity of MS while impregnation had no effect. This had an incidence on indomethacin release rate, which was assessed using the rapid elution of PBS through loaded impregnated MS packed in a column. Indomethacin loading reduced its own rate of release. MS impregnated with 2% w/v alginate gelled with a 40 mM calcium solution presented the lower release rate. This work indicated the manufacturing conditions to display a calcium alginate matrix effect on indomethacin release from DEAE-Trisacryl MS.  相似文献   

17.
A surface-modified silica gel was produced to improve the surface affinity to an oily medicine, phytonadione (VK1). The effect of the degree of surface modification of the silica gel on the drug release behavior from the silica porous matrix was investigated. The silica gels were surface-modified using the silan coupling agent, 3-methacryloxypropyltrimethoxysilane (C7), octadecyltriethoxysilane (C18), or 3,3,3-trifluoropropyltrimethoxysilane (F3). A mixture of VK1 solution and surface-modified silica gel was evaporated under reduced pressure at room temperature, then the resulting powder was dried in vacuo. The degree of surface modification was evaluated based upon elementary analysis. The dissolution profiles of the samples were investigated in Japanese Pharmacopoeia XII, 1st fluid buffer (pH 1.2, 37+/-0.5 degrees C) containing 1.5% sodium lauryl sulfate. The FT-IR spectra of VK1-loaded surface-modified silica gels suggested that the amount of hydrogen-bonded VK1 with the silanol group on the gel surface decreased with increasing hydrophobicity of the silica gel. Since the modified group was rotating on the silica gel surface, and inhibited the adsorption of VK1 to the surface, the attractive molecular interaction between VK1 and the silica gel surface might decrease with increasing length of the modified functional group. However, the characteristics of the affinity of VK1 to the functional groups significantly differed among the groups. The VK1 release from the modified silica gels was initially rapid, slowed markedly after 1 h, and continued for more than 24 h. The amount of VK1 released from the modified surface silica gels by C7, C18 or F3 increased with increasing density of the surface modification group. The mean drug release moment (MDT) decreased with an increase in surface-modified group density.  相似文献   

18.
The objective of this study was to use the polymer, carrageenan (Gelcarin, GP 812) in an attempt to control the drug release from spheres prepared by cross-linking technique. The variables studied were the drug levels; polymer levels and the cross-linking agent. The aqueous dispersion of the drug and polymer was dropped by a disposable syringe into 3% w/v aqueous solution of cross-linking agent, and the droplets instantaneously formed spheres. Spherical agglomerates containing 77.6% w/w drug could be prepared and the physical properties of the spheres was dependent on the drug and polymer levels and also on the cross -inking material used. The drug release from spheres containing 11.9% w/w drug prepared by using 3% w/v cross-linking agent was higher than those containing 77.6% w/w drug. Carrageenan polymer can exert control over the rate and amount of drug released from spheres prepared by cross-linking technique.  相似文献   

19.
Magnetite containing aerogels were synthesized by freeze-drying olive oil/silicone oil-based Janus emulsion gels containing gelatin and sodium carboxymethylcellulose (NaCMC). The magnetite nanoparticles dispersed in olive oil are processed into the gel and remain in the macroporous aerogel after removing the oil components. The coexistence of macropores from the Janus droplets and mesopores from freeze-drying of the hydrogels in combination with the magnetic properties offer a special hierarchical pore structure, which is of relevance for smart supercapacitors, biosensors, and spilled oil sorption and separation. The morphology of the final structure was investigated in dependence on initial compositions. More hydrophobic aerogels with magnetic responsiveness were synthesized by bisacrylamide-crosslinking of the hydrogel. The crosslinked aerogels can be successfully used in magnetically responsive clean up experiments of the cationic dye methylene blue.

Magnetite containing aerogels were synthesized by freeze-drying olive oil/silicone oil-based Janus emulsion gels containing gelatin and sodium carboxymethylcellulose (NaCMC).  相似文献   

20.
The encapsulation of biofunctional compounds, release properties and targetability of polymersomes of amphiphilic block-copolymers based on poly(ethylene glycol) (PEG) and biodegradable polyesters or polycarbonate are described. Carboxyfluorescein (CF), as a model for hydrophilic biofunctional compounds, could be readily incorporated in the polymersomes by adding the compound to the aqueous phase during polymersome preparation. The release of encapsulated material from the polymersomes can be adjusted by changing the copolymer composition, especially the molecular weight and type of hydrophobic block of the copolymer. The presence of plasma proteins other than albumin suppressed the release of CF. CF release in PBS both at room temperature and at 60 degrees C followed first order kinetics, confirming that the CF containing polymersome system is a membrane controlled reservoir system. These biodegradable polymersomes have the potential to be targeted to specific sites in the body as shown by the specific interaction of anti-human serum albumin immobilized polymersomes with a human serum albumin coated sensor surface.  相似文献   

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