Hysteresis in the glucose permeability versus pH characteristic for a responsive hydrogel membrane

A side-by-side diffusion cell was used to study the permeability of glucose through a temperature- and pH-sensitive poly(N-isopropylacrylamide-co-methacrylic acid) hydrogel membrane. At fixed temperature (37°C), lowering pH in one side of the cell induced hydrogel volume collapse and strongly attenuated glucose permeation across the membrane. Hysteresis was observed in the glucose permeability versus pH characteristic.     

Drug release from hydrogel devices with ratecontrolling barriers

Zero order release of a drug from monolithic polymer devices fails because the drug concentration gradient within the matrix falls with time. In principle, it should be possible to maintain this concentration gradient constant via the introduction of a ratelimiting barrier to solute diffusion at the surface of the device. In this study, progesterone-dispersed monolithic devices were prepared from either polyhydroxyethyl methacrylate (HEMA) or a copolymer of HEMA and methoxyethoxyethyl methacrylate (MEEMA). These monolithic devices were soaked in an ethanol solution of ethylene glycol dimethacrylate (EGDMA) followed by exposure to UV light to create a crosslinked zone at the outer edge. The cross-linked zone has a much lower permeability to solute than the central region of the device and therefore serves as a rate-limiting barrier. Progesterone release studies demonstrated a zero order release from devices with the crosslinked outer layer. Drug release rates were dependent upon the UV treatment time, the EGDMA concentration, and the device soaking time in the EGDMA solution.     

Mathematical modeling and sustained release property of a 5-fluorouracil imprinted vehicle

In the present research, a type of imprinted hydrogels, in which 5-fluorouracil is complexed non-covalently to the monomers and cross-linked into the hydrogel matrix, is synthesized in order to evaluate the possibility of their applications in sustaining the release of 5-fluorouracil due to the drug’s heightened interactions with the imprinted binding sites. Because of the hydrophility, hydrogels can absorb large amounts of water. As a result, drug release mechanisms are different from hydrophobic polymers. Mathematical model has been established to predict the drug release from the hydrogel matrix as a function of time. The drug release mechanism when immersed in release medium is discussed based on mathematical analysis. Swelling studies are performed and the capability of the hydrogels to reload 5-fluorouracil in aqueous solutions is evaluated. In vitro release studies after reloading are conducted. Mathematical analysis suggest that drug release kinetics from the hydrogels fit Fickian mechanism, further evaluation of the fitness for different hydrogel types reveal that the conformation of binding sites can play a very important role in deciding the kind of drug release mechanism. Experiments reveal that all hydrogels show swelling property. The imprinted hydrogels bind much more 5-fluorouracil than non-imprinted ones, and they sustain 5-fluorouracil release better than non-imprinted hydrogels. This research indicates that the imprinted hydrogels would be a potential promising device for drug delivery.     

Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from kappa-carrageenan hydrogel device by surface erosion of the hydrogel

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and kappa-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and kappa-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of kappa-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry kappa-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of kappa-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93-100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen kappa-carrageenan hydrogel from the surface of the device.     

External control of drug release. IV. Controlled release of 5-fluorouracil from a hydrophilic polymer matrix by microwave irradiation

A polymeric system capable of delivering 5-fluorouracil (5-FU) at increased rates on demand by external microwave irradiation was developed. Sustained-release systems were made by incorporating 5-FU into an ethylene-vinyl alcohol copolymer. When exposed to release medium, the delivery systems released the drug slowly and continuously. Upon exposure to microwave irradiation, the drug was released at a much higher rate. Release rates returned to base line levels when the microwave irradiation was discontinued. This study demonstrated that release rates of 5-FU from a polymer matrix can be increased at desired times by external microwave irradiation.     

Effects of 5-fluorouracil on erythrocytes in relation to its cardiotoxicity: membrane structure and functioning

In the present study, we showed that the antineoplastic drug 5-fluorouracil (5-FU) induces in vitro exposure-time/dose-dependent changes on the level of an erythrocyte's morphology, ionic balance, and membrane fluidity. These changes are partially or fully irreversible, and we suggest that they are provoked by an irreversible depletion of ATP. Because of these changes that could also occur in vivo during 5-FU infusion, a certain amount of erythrocytes with echinocytic shape and diminished ability to deliver oxygen is present in blood for longer periods of time. This renders oxygen transport and delivery more difficult, leaving the heart with an insufficient supply of oxygen, thus leading to cardiotoxicity.     

Molecular structure of 5-fluorouracil from gas-phase electron diffraction data and quantum-chemical calculations

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Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from κ-carrageenan hydrogel device by surface erosion of the hydrogel

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and κ-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and κ-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of κ-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry κ-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of κ-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93–100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen κ-carrageenan hydrogel from the surface of the device.     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

Effect of tretinoin inclusion in dimethyl-beta-cyclodextrins on release rate from a hydrogel formulation

The aim of this work was to study the release, permeation and skin retention profiles of 0.05% tretinoin hydrogel formulations in which tretinoin was in free form or complexed with dimethyl-beta-cyclodextrin in a stoichiometry of 1:4. Theoretically, this complexation will mainly allow to: overcome drug’s low water solubility and low stability; enhance the drug permeation by promoting skin absorption and alleviate drug inducing local irritation. In vitro release, permeation and skin retention tests were performed in both formulations in order to compare the main advantages of this complexation. The influence of the thermodynamic activity on the drug release profile was also investigated. This study proved that tretinoin inclusion complexes formulation with excess of cyclodextrins had better release profile than the free tretinoin formulation. It was concluded that in this study, thermodynamic activity was not the driving force for the release rate improvement observed with cyclodextrins. Probably, this improvement was due to the increased availability of tretinoin near the membrane surface. In fact, the percentage of total drug that had been retained in the skin was 0.41?±?0.08% for complexed tretinoin gel and 0.17?±?0.04% for the free tretinoin gel.     

Core‐shell structure microcapsules with dual pH‐responsive drug release function

We report dual pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)‐shell (chitosan) structure with dual pH‐responsive drug release function. The fabricated core‐shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core‐shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core‐shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core‐shell microcapsules were a potential candidate of dual‐drug carriers.     

Fabrication of a high-strength hydrogel with an interpenetrating network structure

Hydrogels have potential applications in many fields, but the poor mechanical strength has limited their further development. In this article, we designed a high-strength hydrogel with an interpenetrating network (IPN) structure from polyacrylamide (PAM) and poly(vinyl alcohol) (PVA). Synthesis parameters, such as PVA/AM mass ratio, crosslinker dosage and elongation time were carried out for high tensile strength and elongation. The results showed that chemical crosslinking, physical entanglement and PVA precipitates were the dominant parameters for the improvement of mechanical properties. The PVA structure transferred from crystal to amorphous due to intermolecular and intramolecular interactions (such as hydrogen bond and self-crosslinking). PVA precipitates scatterred in the brittle PAM matrix homogeneously which dispersed the applied stress and improved the hydrogel toughness. The tensile strength and elongation were extremely high, they were 2.4 MPa and 3100%, respectively. The simple method is versatile in synthesizing high-strength IPN hydrogels using many kinds of polymer species.     

Methylprednisolone release from agar-Carbomer-based hydrogel: a promising tool for local drug delivery

A number of studies and works in drug delivery literature are focused on the understanding and modelling of transport phenomena, the pivotal point of a good scaffold design for tissue engineering. Accurate knowledge of the diffusion coefficient of an active drug plays a key role in the analysis, prediction of their kinetics and formulation of efficient drug delivery systems. In this work, the kinetics of the release of methylprednisolone from agar-Carbomer hydrogel were studied taking into consideration the different drug concentrations and clearances typically achieved in in vitro or in vivo tests. Starting from the experiments it is possible to model the transport phenomenon and to calculate the diffusion coefficient through the hydrogel matrix.     

Synthesis and characterization of ramose tetralactosyl-lysyl-chitosan-5-fluorouracil and its in vitro release

In order to improve drug loading and achieve a good release effect, this paper adopts the ramose method, choosing chitosan as the carrier and 5-fluorouracil (5-Fu) as a model drug. Ramose chitosan-lysyl-5-Fu(3) and ramose tetralactosyl-lysyl-chitosan-5-Fu(6) were synthesized successfully, then the in vitro release of (6) was researched. The results show that the drug loading of (3) and (6) are 9.17 and 1.63% (w/w), respectively. The in vitro release behavior of (6) in pH 7.4 phosphate buffer solution and pH 1.2 HCl?CKCl solution were studied. The zero order release time that (6) maintains in alkaline and acidic media are 64 and 24?h, and the total release by 184?h are 71.97 and 82.34%, respectively. The performance is smooth throughout the whole stage of release, and the concentration of cumulative release is lower in the alkaline environment than in the acidic environment over the same time.     

Interaction of 5-fluorouracil with sodium carboxymethylcellulose

The interaction of an anticancer drug, 5-fluorouracil with sodium carboxymethylcellulose in aqueous solution was studied with a spectral method and viscosity measurement. From the binding data, the standard molar change in enthalpy, entropy and the number of binding sites on polymer were calculated. The standard molar change of enthalpy of 5-fluorouracil is about — 7 Kcal/mol with sodium carboxymethylcellulose. The enthalpy change is a considerably greater.     

温敏性PNIPAAm水凝胶对布洛芬的控制释放

采用自由基聚合法在水溶液中制备了温敏水凝胶聚N-异丙基丙烯酰胺(PNIPAAm),以非水溶性药物布洛芬(IBU)为模型药物分子,研究了该水凝胶的温敏性能及与药物IBU的相互作用,考察了不同温度下(25 ℃和37 ℃)IBU在磷酸盐缓冲溶液(PBS,pH=7.4)中的释放行为.研究结果表明:该水凝胶的最低临界溶解温度(L...     

Evaluation of retention and release processes of two antibiotics from the biocompatible core-shell microparticles

By dropwise addition of a chitosan solution into different non-solvent, such as: 1 N and 2 N NaOH as well as 1 N NaOH: C₂H₅OH mixture (2:1, v/v) at temperature of 25 °C and 50 °C under stirring, the spherical pure chitosan microparticles were performed. As solvents for chitosan was used 0.1 N acetic acid or 0.1 N HCl. The immersion of the pure chitosan microparticles in hyaluronan solution led to complex microparticles, namely chitosan microparticles covered by a hyaluronan layer. For all the microparticles performed the behaviours in the retention process of two antibiotics: chloramphenicol succinate sodium salt and cefotaxime sodium salt were analyzed. Also, the study shows the release behaviour of cefotaxime sodium salt by the microparticles loaded with this drug. Among the microparticles performed a type of complex microparticles can be considered a suitable drug delivery system for cefotaxime. These microparticles were performed by dropwise addition of chitosan solution in 0.1 N acetic acid into the 1 N NaOH: C₂H₅OH (2:1, v/v) non-solvent at 20 °C for 3 h, followed by their washing up to alkalinity loss and the immersion in hyaluronan solution of 10 g/L concentration for 24 h.