麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

Colon-specific devices based on methacrylic functionalized Tween monomer networks: Swelling studies and in vitro drug release

Colon-targeted delivery devices based on methacrylic functionalized Tween monomer networks, useful for 5-FU or Ferulic acid site-specific release, were synthesized. The basic design consists of methacrylic functionalized Tween monomer-based networks prepared with or without acrylic acid as co-monomer. The swelling behaviour and loaded drugs release from these gels was studied as a function of pH. The devices showed a strong pH-dependent swelling behaviour, allowing a maximum release at pH 7.4. The acrylic acid introduction increased the polymeric gels pores size, as evidenced by the loading efficiency increase, but also reduced the amount of released drug in basic media compared to analogous network not containing the co-monomer. This behaviour, already found in the matrix swelling, could be attributed to a slower hydrolysis kinetics of the ester bond in functionalized Tween monomers, which implies a reduced ability to absorb water from a basic medium, resulting in a lower capacity to release the loaded drug.Since our device possesses a maximum drug release in the media at pH 7.4, it could be used for colon-targeted drug delivery of both 5-FU and Ferulic acid.     

Effects of intercalated hydrotalcite on drug release behavior for poly(acrylic acid-co-N-isopropyl acrylamide)/intercalated hydrotalcite hydrogels

The influence of positively charged intercalated hydrotalcite (IHT) in the anionic poly(acrylic acid-co-N-isopropyl acrylamide), poly(AA-co-NIPAAm)/hydrotalcite nanocomposite hydrogels on the drug release behavior for the drugs with different charges was investigated in this study. Results show that the loading amount and release ratio of indomethacin are affected by the swelling ratio in saline solution and related to the affinity in the alcohol solution, respectively. The loading amount and release ratio of caffeine are affected by the swelling ratio. The loading amount of crystal violet (CV) increased with an increase of the content of intercalating agent in IHT of the gel but the fractional release of CV in the gels decreases with increase in intercalating agent content. The result of release and loading for phenol red in the hydrogels is contrary to CV.     

In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.     

Loading and release of charged dyes using ultrathin hydrogels

The anionic dyes methyl orange (MO) and allura red (AR) were used as model drugs to assess the loading and release by layer-by-layer assembled ultrathin hydrogels prepared via the amide formation of poly(acrylic acid-co-N-isopropylacrylamide) with AAc contents of 5, 10, and 15 mol % plus poly(vinylamine hydrochloride). The amount of MO loaded was potentially controlled by changing the dye concentrations, film thickness, and AAc content of the copolymers. The release of AR was controlled by the NaCl concentration and pH. We conclude that the polymeric matrices of ultrathin hydrogels have great potential for the loading and release of charged drugs.     

The Influence of Temperature and Drug Concentrations Prednisolone in NIPAAm Copolymer

Controlled delivery systems would be more beneficial and ideal if the drug could be delivered with respond to external environmental change. It could be used to overcome the shortcomings of conventional dosage forms. Therefore, the correct amount of drug would be released upon the stimulation of such a temperature and concentration change. The purpose of study is to investigate the influence of temperature and drug concentration from poly(2-hydroxyethyl methacrylate and N-isopropylacrylamide)/poly(HEMA-NIPAAm). The macroporous structure 5HEMA15NIPAAm was showed the most rapid responsiveness in swelling ratio, polymer volume fraction, swelling and deswelling kinetics. The high drug loading capacity was achieved at or below ambient temperature, whilst the release profile was revealed sustain release of conventional anti-inflammatory drug; prednisolone 21 hemisuccinate sodium salt. In general, drug loading capacity and drug diffusion kinetics are influence by the porosity of hydrogels, temperature, and drug concentration.     

Preparation of Highly Loaded PAA/PAH Layer-by-layer Films by Combining Acid Transformation and Templating Methods

Enhancing the molecular loading capability of layer-by-layer(LbL)method holds high importance in environmental and biomedical application.Here,we reported a strategy to prepare highly loaded poly(acrylic acid)(PAA)/poly(allylamine hydrochloride)(PAH)LbL films by combining the particulate templating strategy and acid treatment film transformation and realized tlae efficient loading of hydrophilic small molecules.The loaded molecules can be released in a pH-controlled manner.A slow release speed was observed in the acidic solutions with pH value of 3.Abrupt releases were observed at higher pH values(5 or 7).     

Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1 : 1 and 1 : 5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 n HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1 : 5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1 : 5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r(2)=0.9808).     

The pH stimulated reversible loading and release of a cationic dye in a layer-by-layer assembled DNA/PAH film

Through the layer-by-layer (LbL) deposition method, DNA was assembled into an ultrathin film with a cationic poly(allylamine hydrochloride) (PAH). The loading and release of a typical cationic dye, 5, 10, 15, 20-tetrakis(4-N-methylpyridyl)porphine-tetra-(p-toluenesulfonate) (TMPyP), in the DNA/PAH films were investigated. It has been found that the LbL-assembled DNA/PAH film was very stable in both acidic and alkaline solutions. Stimulated by the pH change of the dye solution, the dye can be easily loaded into or released from the DNA/PAH film. In an alkaline solution, the dye could be rapidly loaded into the DNA/PAH film at room temperature, while in an acidic solution, the dye could be rapidly released. The mechanism of such pH-stimulated loading and release in the DNA/PAH film was discussed. It was further observed that the loading and release of the dye in the DNA/PAH film was reversible upon pH change and the process could be repeated many times.     

Controlled drug release from gels using lipophilic interactions of charged substances with surfactants and polymers

The aim of this article was to study interactions between different gel forming polymers and amphiphilic drugs and surfactants with the intention of finding interactions that can be used for designing controlled release formulations. The release from gels was measured by detecting the UV-absorbance of drugs released from 6 mL gel into 250 mL release medium in a dissolution bath. The rheological behavior of gels was characterized using a controlled rate rheometer. The diffusion coefficient of alprenolol was 6.3 x 10(-6) cm(2)/s when formulated in a 1% poly(acrylic acid) gel (PAA) and 2.8 x 10(-6) cm(2)/s in a lipophilically modified gel (LM-PAA). The addition of alprenolol to 1% LM-PAA increased the elasticity, G', from 123 to 182 Pa. Increased gel strength was also observed for a number of other amphiphilic drugs. The addition of 1% Brij 58 to LM-PAA decreased the diffusion coefficient of alprenolol to 2.3 x 10(-6) cm(2)/s. It was possible to sustain the release of charged drugs with high log P by adding surfactant micelles. However, the effect was small and only useful for drugs with adequate lipophilicity. The interaction between LM-PAA and amphiphilic drugs could be seen using rheology and was used for designing controlled release gel formulations. In this way surfactants can be avoided, thus decreasing toxicity problems.     

Stimuli‐Responsive Theragrippers for Chemomechanical Controlled Release

We report on a therapeutic approach using thermo‐responsive multi‐fingered drug eluting devices. These therapeutic grippers referred to as theragrippers are shaped using photolithographic patterning and are composed of rigid poly(propylene fumarate) segments and stimuli‐responsive poly(N‐isopropylacrylamide‐co‐acrylic acid) hinges. They close above 32 °C allowing them to spontaneously grip onto tissue when introduced from a cold state into the body. Due to porosity in the grippers, theragrippers could also be loaded with fluorescent dyes and commercial drugs such as mesalamine and doxorubicin, which eluted from the grippers for up to seven days with first order release kinetics. In an in vitro model, theragrippers enhanced delivery of doxorubicin as compared to a control patch. We also released theragrippers into a live pig and visualized release of dye in the stomach. The design of such tissue gripping drug delivery devices offers an effective strategy for sustained release of drugs with immediate applicability in the gastrointestinal tract.     

Rapid and precise release from nano-tracted poly(N-isopropylacrylamide) hydrogels containing linear poly(acrylic acid)

We investigated the rapid and precise molecular release from hydrogels in response to dual stimuli. To achieve precise on/off drug release using thermoresponsive poly(N-isopropylacrylamide) hydrogels, we prepared nano-structured semi-IPNs, which consisted of thermosensitive PNIPAAm networks penetrated by pH-responsive poly(acrylic acid) (PAAc) linear chains and perforated to create nano-tracts as a molecular pathway. The present nano-tracted semi-IPNs show a rapid deswelling response to both temperature and pH. Model drug releases were investigated when simultaneous changes in temperature and pH were applied. We observed that the cationic drug was rapidly released and then abruptly discontinued from the nano-tracted semi-IPNs in response to the dual stimuli, and clear release and stopping cycles were repeatedly observed on successive steps. Moreover, the release rates and amount of drug released were controllable by the deswelling speed of the gels and the PAAc content inside the gels. This novel release system using the nano-tracted semi-IPNs may be useful for the high performance, pulsed release of molecules.     

Effect of molecular weight and degree of deacetylation on controlled release of isoniazid from chitosan microspheres

Glutaraldehyde cross‐linked chitosan microspheres for controlled release of isoniazid were prepared using chitosan of different molecular weights (MWs) and degrees of deacetylation (DDAs). Chitosan microspheres were characterized for their size, hydrophobocity, degree of swelling and loading of isoniazid. Hydrophobicity of chitosan microspheres increased on increasing the degree of cross‐linking and MW of chitosan. Chitosan microspheres with high degree of deacetylation (DDA) (75 wt%), high MW chitosan (2227 kg mol^?1), and with 12 wt% concentration of glutaraldehyde showed optimum loading and release of isoniazid. The isoniazid from chitosan microspheres was released in two steps, i.e. burst (%R_B) and controlled (%R_C) steps. The microspheres with low MW chitosan (260 kg mol^?1) and low DDA (48 wt%) showed prominent burst release of isoniazid, but microspheres with high MW chitosan (2227 kg mol^?1) and high DDA (75 wt%) have released more isoniazid in a controlled manner (60 wt%) at 37°C in a solution of pH 5.0 ± 0.1. The burst step of drug release (%R_B) has followed first order kinetics, whereas controlled step of drug release (%R_C) followed zero order kinetics. The burst step of drug release was Fickian and controlled step was non‐Fickian in nature. The diffusion constant (D) for isoniazid release was influenced by the properties of chitosan and degree of cross‐linking. Copyright © 2007 John Wiley & Sons, Ltd.     

Monte Carlo simulations of stress relaxation of entanglement-free Fraenkel chains. II. Nonlinear polymer viscoelasticity

The nonlinear viscoelastic behavior of the Fraenkel-chain model is studied with respect to the constitutive equation of the Rouse model. Distinctly different from the results of the Rouse model, the Fraenkel-chain model gives the following characteristic nonlinear behavior: (a) The two distinct dynamic modes in the relaxation modulus GS(t,lambda)--as observed in the linear region reported in Paper I [Y.-H. Lin and A. K. Das, J. Chem. Phys. 126, 074902 (2007), preceding paper]--or in the first normal-stress difference function GPsi1(t,lambda) are shown to have different strain dependences: strain hardening for the fast mode and strain softening for the slow mode. (b) The Lodge-Meissner relation GS(t,lambda)=GPsi1(t,lambda) holds over the whole time range, which has been shown both analytically and by simulation. (c) The second normal-stress difference is nonzero, being positive in the fast-mode region and negative in the slow-mode region. The comparisons between orientation and stress for all tensor components consistently confirm the strong correlation of the slow mode as well as its entropic nature with the segmental-orientation anisotropy as shown in the linear region studied in Paper I. A consequence of this correlation is the applicability of the stress-optical rule in the slow-mode region. This also leads to the expectation that the damping function h(lambda)=G(S)(t,lambda)/G(S)(t,lambda-->0) and the ratio between the first and second normal-stress differences, N2(t,lambda)/N1(t,lambda), are described by the orientation tensor which has the same form as that given by Doi and Edwards [J. Chem. Soc. Faraday Trans. 2 74, 1789 (1978); 74, 1802 (1978)] with independent-alignment approximation for an entangled system. The similarity between the slow mode of an entanglement-free Fraenkel-chain system and the terminal mode of an entangled polymer system as observed in the comparison of theory, simulation, and experiment suggests that the close correlation of the entropic nature of the mode with the orientation anisotropy--as of the Fraenkel segment or the primitive step in the Doi-Edwards theory--is a generally valid physical concept in polymer viscoelasticity.     

Application of a new mathematical method for the estimation of the mean surface area to calculate the percolation threshold of lobenzarit disodium [correction of dissodium] salt in controlled release matrices

One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O((t))). The new method was validated and three novel results were achieved: A constant value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272 cm(2)); a linear relationship between initial surface area (O((0))) and critical time; and a linear relationship between O((t)) and time. Employing the values of O((t)), it was possible to calculate for the first time, the percolation threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.     

Morphological changes of ethylene/vinyl acetate-based controlled delivery systems during release of water-soluble solutes

Thin slabs of theophylline and monomer albumin release systems were prepared by dispersing 212-300 μm and 300-25 μm particles respectively, of these bioactive agents in a methylene chloride solution of ethylene/vinyl acetate (EVAc) copolymer (40 wt% vinyl acetate), and evaporating the solvent at low temperatures according to the Langer—Folkman technique. Compositions containing 21.41 wt%, 31.04 wt% and 40.0 wt% albumin, and 19.32 wt% theophylline were prepared. Solute release experiments were performed in deionized water at 37 ± 0.1°C under perfect-sink conditions. The concentration of released solute was determined by measuring the absorbance of the UV spectra at 276 nm for albumin and 272 nm for theophylline. Both solutes could be released for long periods of time at controlled rates. The main mechanism of release was established to be solute dissolution and diffusion through the generated, waterfilled pore structure. Photomicrographs present the main features of this pore network. Mercury porosimetry was used to determine the pore volume and size of pores for freezedried slabs before, during and after the dissolution/diffusion/release process. Considerable pore collapse was observed and pore diameters of 8-650 μm were detected. In addition to solution diffusion through large pores, diffusion might occur through small constrictions between large pores or through a pore network of much smaller pores created in the matrix.     

Active loading and tunable release of doxorubicin from block copolymer vesicles

Vesicles are spherical bilayers that offer a hydrophilic reservoir, suitable for the incorporation of water-soluble molecules, as well as a hydrophobic wall that protects the loaded molecules from the external solution. The permeability of a vesicle wall made from polystyrene can be enhanced by adding a plasticizer such as dioxane. Tuning the wall permeability allows loading and release of molecules from vesicles to be controlled. In this study, vesicles are prepared from polystyrene(310)-b-poly(acrylic acid)(36) and used as model carriers for doxorubicin (DXR), a weak amine and a widely used anticancer drug. To increase the wall permeability, different amounts of dioxane are added to the vesicle solution. A pH gradient is created across the vesicle wall (inside acidic) and used as an active loading method to concentrate the drug inside the vesicles. The results show that a pH gradient of ca. 3.8 units can enhance the loading level up to 10-fold relative to loading in the absence of the gradient. After loading, the release of DXR from vesicles is followed as a function of the wall permeability. The diffusion coefficient of doxorubicin through polystyrene (D) is evaluated from the initial slope of the release curves; the value of D ranges from 8 x 10(-17) to 6 x 10(-16) cm(2)/s, depending on the degree of plasticization of the vesicle wall.     

Loading and release mechanisms of a biocide in polystyrene-block-poly(acrylic acid) block copolymer micelles

The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the micelles was found to be a two-step process. First, the surface of the PS core of the micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to micelles during transient micelle-biocide contacts. Next, the biocide penetrates as a front into the micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the micelles becomes very slow. Maximum loading of biocide into micelles is approximately 30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a similar preference for polystyrene as for ethylbenzene over water, implying that the maximum loading is governed by thermodynamics.     

Poly (N-isopropylacrylamide)/poly (ethylene oxide) blend nanofibrous scaffolds: thermo-responsive carrier for controlled drug release

A facile electrospinning method has been utilized to fabricate poly (N-isopropylacrylamide) (PNIPAM)/poly (ethylene oxide) (PEO) blend nanofibers having the mean fiber diameters from approximately 250 to 380 nm. Scanning electron microscopy (SEM) images showed that the morphology and diameter distribution of the nanofibrous scaffolds can be easily modulated by changing the weight ratio of PNIPAM/PEO in electrospinning solution. X-ray diffraction (XRD) and thermogravimetric analysis (TGA) demonstrated that there were interactions between the molecules of PNIPAM and PEO. Vitamin B12 was chosen as a hydrophilic model drug for in situ encapsulation in PNIPAM/PEO blend nanofibrous scaffolds. The rate of drug release can be controlled by adjusting the weight ratio of PNIPAM/PEO, the temperature of release medium and the drug loading amount. It is suggested that the blend nanofibrous scaffold could be used as a new thermo-responsive matrix for the entrapment and controlled release of drugs.     

Thermophysical properties and material modelling of acrylic bone cements used in vertebroplasty

The stabilization of osteoporotic vertebrae with acrylic bone cement, called vertebroplasty, is a common procedure in modern surgery. However, the thermomechanical-chemically coupled material behaviour of curing bone cements makes the application even for experienced surgeons difficult and can lead to potential complications like heat necrosis, leaking bone cement, embolisms and postoperative load shifting. In order to reduce these potential complications, to minimize the risks and to better understand the occurring effects, the thermophysical properties of a commercial acrylic bone cement were investigated in detail using differential scanning calorimetry, volumetric dilatometry and temperature controlled rheometry. More specifically, the reaction kinetics, the specific heat, the thermal conductivity, the thermal expansion, the chemical shrinkage as well as the mechanical behaviour was studied during the reaction process of the bone cement. Furthermore, the explored material behaviour is described by a customized material model that takes into account all observed effects. With the aid of this model the inhomogeneous chemical, thermal and mechanical states that appear during the application and curing of acrylic bone cements, can be studied by finite element treatment.