Antibiotic drug release behavior of poly (vinyl alcohol)/sodium alginate hydrogels

Poly (vinyl alcohol)/sodium alginate hydrogels were prepared by freeze-thaw followed by calcium ion crosslinking. Chloramphenicol release behavior from the poly (vinyl alcohol)/sodium alginate hydrogels in mimic conditions of gastrointestinal tract was examined. The effects of composition, number of freeze-thaw cycles and calcium ion concentration on drug release process were investigated. The results showed that the cumulative release amount of chloramphenicol from the hydrogels (crosslinked through 4 freeze-thaw cycles and immersed in 2 % calcium chloride solution) decreased from 84.3 % to 72.3 % as sodium alginate content increased from 0 % to 75 %. For the hydrogels containing 50 % sodium alginate and immersed in 2 % calcium chloride solution after the freeze-thaw cycles, cumulative release amount of chloramphenicol decreased from 83.5 % to 76.6 % as the freeze-thaw cycles increased from 2 to 6. Cumulative release amount of chloramphenicol from the hydrogels containing 50 % sodium alginate and with 4 freeze-thaw cycles decreased from 79.8 % to 75.6 % when concentration of calcium chloride solution increased from 1 % to 4 %.     

Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

Artificial tissue engineering scaffolds can potentially provide support and guidance for the regrowth of severed axons following nerve injury. In this study, a hybrid biomaterial composed of alginate and hyaluronic acid (HA) was synthesized and characterized in terms of its suitability for covalent modification, biocompatibility for living Schwann cells and feasibility to construct three dimensional (3D) scaffolds. Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calcium ions that ionically crosslink alginate. Amide formation was found to be dependent on the concentrations of carbodiimide and calcium chloride. The double-crosslinked composite hydrogels display biocompatibility that is comparable to simple HA hydrogels, allowing for Schwann cell survival and growth. No significant difference was found between composite hydrogels made from different ratios of alginate and HA. A 3D BioPlotter^TM rapid prototyping system was used to fabricate 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.     

Preparation and characterization of silk fibroin hydrogel as injectable implants for sustained release of Risperidone

The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1?min, while the gelation time of HCL/acetone-based hydrogels was around 360?min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25?d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone.     

PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

A covalently crosslinked polysaccharide hydrogel for potential applications in drug delivery and tissue engineering

The development of non-cytotoxic hydrogels that can allow for the controlled release of molecules has important clinical and therapeutic applications. In this paper, we developed a series of in situ hydrogels by combining N,O-carboxymethyl chitosan and oxidized alginate without additional crosslinking agents. The rheological properties of these hydrogels as well as their gelling time, swelling ratio, and in vitro degradation behavior were investigated. We observed that although gelation was rapid at physiological temperature, it was even faster in the presence of higher oxidization degree of alginate. In vitro cytotoxicity study showed that the developed hydrogels were not cytotoxic after 24?h of culturing with NIH-3T3 cells. Additionally, bovine serum albumin was released from the hydrogels initially by diffusion at early stages followed by a degradation-dependent mechanism at later stages. In conclusion, the developed hydrogel might have potential application in the drug delivery system and tissue engineering.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Kinetics and Mechanism of Drug Release From Calcium Alginate Membrane Coated Tablets

Compressed tablets containing guaifenesin (model drug), calcium acetate (reactant) and pharmaceutical excipients were prepared. The tablets were coated with calcium alginate hydrogel using a novel, self-correcting membrane coating technique. Effects of coating time, the type of alginate polymer and pH of the dissolution medium on the rate of drug release were evaluated. In distilled water, zero order drug release profiles were obtained from the coated tablets. The release rate decreased with an increase in the coating time (increased coat thickness) and molecular weight of alginate polymer. The release rate constants correlated with model for spherical reservoir system and, were used to calculate permeability of guaifenesin in the calcium alginate coatings. Alginate polymer with higher guluronic acid content provided acid stable coating and higher molecular weight polymer produced membrane with lower permeability for guaifenesin.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Investigation of charge effects on drug release behavior for ionic thermosensitive hydrogels

The influence of various drugs with different charges on the drug release behavior in porous ionic thermosensitive hydrogels was investigated. The present hydrogels were prepared from N-isopropylacrylamide (NIPAAm) and cationic monomer, trimethyl (acrylamido propyl) ammonium iodide (TMAAI), or anionic monomer, acrylic acid (AA), or zwitterionic monomer, N′,N′-dimethyl (acrylamido propyl) ammonium propane sulfonate (DMAAPS), or nonionic monomer, poly(ethylene glycol) methylether acrylate (PEGMEA), and pore-forming agent, poly(ethylene glycol) (PEG) with different molecular weights. Caffeine as a nonionic drug, crystal violet (CV) as a cationic drug solute, and phenol red as an anionic drug solute were chosen as model drugs to perform the drug release experiment. Results show that the release ratio of caffeine in the hydrogels is not affected by the ionicity of hydrogels. The CV strongly interacted with the anionic hydrogel; thus, the CV release ratio is very low. CV is only adsorbed on the skin layer of the cationic hydrogel due to charge repulsion and is released rapidly. The result of phenol red (anionic solute) release in the hydrogels is contrary to CV. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

基于电诱导沉积方法制备海藻酸钙水凝胶

海藻酸钙水凝胶是一种具有良好生物相容性、生物降解性的生物医用高分子材料,但是传统制备方法不能得到具有生理结构的水凝胶。文中提出了一种基于电诱导沉积原理,使用海藻酸钠和碳酸钙混合溶液制备海藻酸钙水凝胶的方法。在分析电诱导沉积原理基础上,搭建了海藻酸钙水凝胶3D打印系统。建立了海藻酸钙水凝胶截面宽度模型,提出了通过调节打印喷头的移动速度控制凝胶截面宽度的方法。应用该系统打印了圆管形、正六边形及四叶草形的生物支架,并用这些结构的生物支架进行细胞培养实验,获得具有一定生物活性的细胞。     

可生物降解温敏凝胶PNMH-OSA的降解行为与释药性能

N-异丙基丙烯酰胺(NIPA)和丙烯酸甲酯(MA)通过自由基共聚形成线型大分子P(NIPA-MA),再用联胺取代MA嵌段上的甲氧基,得到一种多官能团的温敏大分子聚(N-异丙基丙烯酰胺-丙烯酸甲酯-丙烯酰肼)(PNMH),用它交联氧化的海藻酸钠(OSA),得到可生物降解的温敏凝胶PNMH-OSA。研究了PNMH的取代度(DS)、海藻酸钠的氧化程度(DO)、pH值和离子强度对PNMH-OSA凝胶降解性能的影响,同时以次甲基蓝(MB)和牛血清蛋白(BSA)为模拟药物,采用包埋法将药物载入凝胶中,研究了凝胶的释药行为。结果表明,凝胶降解速率随海藻酸钠的氧化程度、pH值增加而增加,随PNMH的取代度、离子强度增加而减慢;药物释放速率与药物的分子量和凝胶的降解速率有关。     

Effects of crosslinking ratio,model drugs,and electric field strength on electrically controlled release for alginate-based hydrogel

The drug release characteristics of calcium alginate hydrogels, (Ca-Alg), under an electric field assisted transdermal drug delivery system were systematically investigated. The Ca-Alg hydrogels were prepared by the solution-casting using CaCl₂ as a crosslinking agent. The diffusion coefficients and the release mechanism of the anionic model drugs, benzoic acid and tannic acid, and a cationic model drug, folic acid on the Ca-Alg hydrogels were determined and investigated using a modified Franz-Diffusion cell in an MES buffer solution of pH 5.5, at a temperature of 37°C, for 48 h. The influences of the crosslinking ratio, —the mole of the crosslinking agent to the mole of the alginate monomer—mesh size, model drug size, drug charge, electric field strength, and electrode polarity were systematically studied. The drug diffusion coefficient decreased with an increasing crosslinking ratio and drug size for all of the model drugs. The drug diffusion coefficient is precisely controlled by an applied electric field and the electrode polarity depending on the drug charge, suitable for a tailor-made transdermal drug delivery system.     

In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents

One of the important routes of drug administration for localized delivery of contraceptives and cervical cancer treatment agents is vaginal canal. Due to the low pH of vagina, a pH-responsive drug delivery system was developed. This hydrogel was synthesized based on a mucoadhesive biopolymer, chitosan (CS), that promotes the interaction between the hydrogel and mucosal surface of the vagina, potentially increasing the residence time of the system. This injectable hydrogel was formed via acid-labile Schiff-base linkages between free amine groups and aldehyde functionalities on modified chitosan. A novel approach was taken to add aldehyde functionalities to chitosan using a two-step reaction. Two types of slow and fast degrading hydrogels were prepared and loaded with iron (II) gluconate dihydrate, a non-hormonal spermicide, and doxorubicin hydrochloride, an anti-cancer drug. The release profiles of these drugs at different pH environments were assessed to determine the pH-dependent release mechanism. Mechanical properties, swell-ability and degradation rate of these matrices were studied. The cross-linking density of the hydrogel as well as pH changes played an important role in the characteristic of these hydrogels. The hydrogels degraded faster in lower pH, while the hydrogel with lower cross-linking density showed longer gelation time and faster degradation rate compared to the gel with higher cross-linking density. In vitro cytotoxicity assessment of these hydrogels in 48?h indicated the non-toxic effect of these hydrogels toward mesenchymal stem cells (MSCs) in the test period.

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温度/pH敏感性Semi-IPN水凝胶的制备与性能

以N-乙烯基乙酰胺（NVA）、醋酸乙烯酯（VAc）和甲基丙烯酸-N,N′-二甲氨基乙酯（DMAEMA）为原料,通过自由基聚合制备了PDMAEMA/P（NVA-co-VAc）半互穿网络（Sem-iIPN）水凝胶。实验结果表明,该水凝胶具有较好的温度敏感性、pH敏感性、溶胀-退胀可逆性。随着温度的逐渐升高,凝胶的溶胀率随之...     

A comparative study of chitosan and poloxamer based thermosensitive hydrogel for the delivery of PEGylated melphalan conjugates

Abstract

Objective: Although the melphalan (ML) used extensively for the management of breast cancer, its clinical application is limited due to significant hemolytic activity. In the present work, a comparative analysis of two distinct in situ-based thermogelling polymers of PEGylated ML was performed.

Methods: Briefly, the PEGylated conjugate of the melphalan (MLPEG 5000) for local and sustained drug release action is loaded into two different thermogelling polymeric systems, namely chitosan- and poloxamer-based systems. The synthesized conjugate was loaded to a chitosan (MLP 5000) and poloxamer-based (MPX-CG) thermogelling injectable hydrogels. These thermogelling hydrogels were evaluated for in vitro hydrolysis, in vitro hemolytic activity. and in vitro anticancer activity.

Results: The lower percent cumulative hydrolysis was witness for both the hydrogels. MPX-CG and MLP 5000 hydrogels as predicted had shown lower percent cumulative hydrolysis of 3.31?±?0.1 and 1.67?±?0.1 after 6?h. The percentage hemolysis of MPX-CG and MLP 5000 even at a concentration of 32?µg/ml was found to be 39.23?±?1.24% and 34.23?±?2.24%, observed at 1?h, respectively. Both the hydrogels showed similar anticancer pattern, the MPX-CG hydrogel showed low cell viability of 8.4?±?1.1% at a concentration of 150?µM and the MLP-5000 hydrogel showed slight higher cell viability (13.12?±?5.4%) as compared with MPX-CG hydrogel.

Conclusion: Hence, from the present study it can be well understood that both the chitosan- and the poloxamer-based thermogelling hydrogel proves to be an effective drug delivery systems for the delivery of the PEGylated conjugates.     

A Sustained Release Drug Delivery System Using Calcium Alginate Beads

Calcium alginate beads impregnated with sulphamethoxazole as model drug were prepared and characterized. Scanning electron microscope was used to examine their surface with and without the drug. The bead average diameter was 1.25mm and the sulphamethoxazole uptake by the beads was about half of the incorporated quantity. The release behaviour was followed using USP dissolution method. The effect on release of factors such as sodium alginate, calcium chloride concentration, pH, hydration and compression were studied. Sodium alginate concentrations had no pronounced effect on the release. The release was found to be a function of calcium chloride concentration. The higher the concentration the lower the release. The smaller the water content the lower the release from the beads. Compression of the beads yields a deformed beads with an increase in their release. Plain calcium alginate beads were not suitable for sulphamethoxazole loading. Sulphamethoxazole diffusion through calcium alginate film was determined. The dissolution patterns were discussed. The system may offer a simple and efficient sustain release preparation.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Release of Ftorafur from pH-sensitive hydrogels with hyperbranched poly(4-vinylbenzyl chloride) moieties

Drug release behavior of a hydrogel is related to its transport mechanism, which is dominated by structure of the hydrogel. Therefore, we prepared pH-sensitive poly(4-vinylpyridine) (P4VP) hydrogels with hyperbranched poly(4-vinylbenzyl chloride) (PVBC; M_n = 2391 g/mol, PDI = 1.87, the minimum percent linearity = 12.4%) moieties (P4VP-PVBC) by atom transfer radical polymerizations (ATRP) in two steps. A PVBC moiety provides the hydrogel with a microenvironment, which may encapsulate guest molecules like drug. The presence of the microenvironment could affect drug transport in the hydrogel matrices. To understand this, we used Ftorafur as drug molecule, and investigated release behavior of the P4VP-based hydrogels. Diffusion and transport mechanism of Ftorafur in the P4VP-based hydrogels was analyzed by early-time and late-time approximation diffusion coefficients. It was found that the transport behavior of Ftorafur was related to the presence of the PVBC moiety and external pH. The presence of the PVBC moiety could sustain release of Ftorafur.     

Reduced Graphene Oxide‐GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering

Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)‐incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO‐GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO‐GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO‐GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high‐fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.