Attempts to control the release of the dyestuff proflavine hemisulphate from calcium alginate gels—I: Physical co-entrapment of polymers

Calcium alginate gel pellets were prepared under various conditions some of which included the incorporation of small amounts of proflavine hemisulphate (PHS). The release of this dyestuff into water was readily monitored by using its high absorption at 445 nm. The highly swollen pellets were constituted almost completely of water held together by a small amount of calcium alginate. It was found that using different concentrations of sodium alginate or co-entrapment of a number of homopolymers into the pellets caused only small variations both in the amount of proflavine hemisulphate released and its rate of release.     

Hydrophobically modified alginate for extended release of pharmaceuticals

Hydrophobically modified alginate hydrogels have great potential in drug delivery as they are biologically compatible and cost efficient. While previous works have shown successful protein, and hydrophobic and hydrophilic drug delivery, little information regarding the relationship between crosslinker density and drug release rate is known. This paper investigates the impact of crosslinker density and hydrophobic degree of substitution within modified alginate gels and solutions on the release kinetics using model hydrophobic drug, sulindac. Near zero‐order release was obtained for an extended period of 5 days. Drug release rates decreased as the crosslinker density within both modified alginate hydrogels and solutions increased. Release data fit well to a simplified Fickian relationship, suggesting that the release mechanism is diffusion‐limited. These release characteristics also correlate with bulk rheological measurements, indicating a strong interrelationship between the mechanical properties and the drug release characteristics of the hydrogels.     

The immobilization of antineoplastic drug cyclophosphamide in calcium alginate

IR spectroscopy and scanning electron microscopy were used for the study of formation of calcium alginate particles. The synthesis was carried out in an aqueous medium via reaction between sodium alginate and calcium chloride. It was found that calcium alginate particles with a homogeneous and dense structure were formed at concentrations 2 wt % and 0.1 M of sodium alginate and calcium chloride, respectively. Formation of calcium alginate particles in the systems containing chitosan was accompanied by the emergence of an adsorption layer of chitosan on the particle surface. The thickness of this layer increased with the enhancement of chitosan concentration. The release kinetics of cyclophosphamide from calcium alginate particles in physiological solution in vitro was investigated. The results showed that such factors as elevated temperature at the drying of calcium alginate particles, the increase in the amount of guluronate in the initial sodium alginate, and thickening of the chitosan adsorbed layer led to a significant decrease in the release rate.     

Extended release of Gliclazide from highly stabilized calcium alginate/poly(acrylamide) beads for diabetes management

In the present work, stability of calcium alginate beads has been remarkably improved by a novel strategy which consists of in situ formation of poly (acrylamide) within the calcium ions cross-linked sodium alginate beads. The resulting beads have been found to be stable for more than 48 h, in the physiological fluid (PF) of pH 7.4, while the plain alginate beads disintegrated within a couple of hours. The release of the anti-diabetic drug Gliclazide (Glz) from the beads was investigated under physiological conditions. The enhanced stability and prolonged release was also confirmed by an in vivo study on Albino Wistar rats.     

海藻酸钠的疏水改性及释药性能研究

为了提高对疏水性药物的负载量和缓释作用,将海藻酸钠氧化后与十二胺反应使其进行疏水改性.对改性后聚合物结构进行了表征.研究了聚合物在水溶液及盐溶液中的粘度变化;将聚合物分散于NaCl/CaCl2的混合溶液中制备成凝胶微球,对药物布洛芬进行了包埋释放实验.结果表明,疏水改性后的海藻酸钠粘度增加,其凝胶微球对布洛芬负载量提高,具有较好的缓释作用.     

Development and evaluation of a monolithic floating drug delivery system for acyclovir

Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200?mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1?N HCl (pH 1.2) at 37±0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ(max)=259?nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30?s and a duration of floating time of 24?h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.     

Polypeptidic Micelles Stabilized with Sodium Alginate Enhance the Activity of Encapsulated Bedaquiline

The coating of polypeptidic micelles with sodium alginate is described as a strategy to improve the stability of micelles for drug delivery. Bedaquiline, approved in 2012 for the treatment of multidrug resistant tuberculosis, has been used as an example of hydrophobic drug to study the loading efficiency, the release of the encapsulated drug in different media, and the in vitro antimicrobial activity of the system. Alginate coating prevents the burst release of the drug from micelles upon dilution and leads to a sustained release in all tested media. In view of possible oral administration, the alginate coated micelles show better stability in gastric and intestinal simulated media. Notably, the encapsulated bedaquiline shows increased in vitro activity against Mycobacterium tuberculosis compared to free bedaquiline.     

Drug release of pH/temperature-responsive calcium alginate/poly(N-isopropylacrylamide) semi-IPN beads

A series of semi-interpenetrating, polymer network (semi-IPN), hydrogel beads, composed of calcium alginate (Ca-alginate) and poly(N-isopropylacrylamide) (PNIPAAM), were prepared for a pH/temperature-sensitive drug delivery study. The equilibrium swelling showed the independent pH- and thermo- responsive nature of the developed materials. At pH=2.1, the release amount of indomethacin incorporated into these beads was about 10% within 400 min, while this value approached to 95% at pH=7.4. The release rate of the drug was higher at 37 degrees C than that at 25 degrees C and increased slightly with increasing PNIPAAM content. These results suggest that the Ca-alginate/PNIPAAM beads have the potential to be used as an effective pH/temperature sustainable delivery system of bioactive agents. [GRAPHS: SEE TEXT] A summary of the temperature- and pH-dependence on the release of the drug over a period of 450 min. The effect of the temperature on the swelling of the beads is shown in the inset.     

Fabrication,characterization, and drug release study of vitamin C–loaded alginate/polyethylene oxide nanofibers for the treatment of a skin disorder

Pigmented purpuric dermatosis (PPD) is a skin disorder mainly seen in the lower limbs. The nanofibrous web has been shown to be an appropriate alternative for the treatment of skin diseases as a drug delivery vehicle. In this study, sodium alginate (SA)/polyethylene oxide (PEO) nanofibers containing vitamin C (VC) were fabricated using both blended electrospinning and core/shell electrospinning. The resultant nanofibers were characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. Enhancing the VC content resulted in increasing the nanofibers diameter. Also, the degradation rate and drug release were investigated. Drug release was evaluated using the in vitro dissolution and permeation method. The degradation rate and the drug release of the core/shell nanofibers were found to be lower than those of the blended nanofibers. The drug release of the extended nanofibers followed a different pattern, indicating that the extension of the nanofibers could be a promising way to control the drug release.     

基于天然高分子基元的阻隔层对磁性载药聚乳酸微球的控释作用

利用层层组装技术构建了基于天然高分子壳聚糖和海藻酸钠的阻隔层, 并研究了该阻隔层对磁性载药聚乳酸微球的药物释放作用. 实验结果表明, 阻隔层能够有效抑制模型药物的突释, 具有延缓药物释放的效果. 具有阻隔层的磁性载药体系具有药物释放平缓和生物相容性高等特点, 是理想的磁靶向载药体系.     

Novel mucoadhesive carriers based on alginate-acrylamide hydrogels for drug delivery

New mucoadhesive two-component carriers for drug delivery based on synthetic acrylamide/diethylacrylamide and natural alginate hydrogels have been synthesized. The introduction of sodium alginate into polyacrylamide/ poly(diethylacrylamide) gels, followed by their crosslinking with metal ions, significantly changed structure and properties of hydrogels, such as swelling degree, drug capacity and drug release rate in physiological solution. The structure of the gels was characterized by FTIR spectroscopy and scanning electron microscopy.     

丁烯氟虫腈缓释微胶囊的制备及其性能

以丁烯氟虫腈为囊芯化合物,带有相反电性的壳聚糖和海藻酸钠为囊壁材料,采用层层自组装技术制备了丁烯氟虫腈微胶囊,通过流点法筛选出十二烷基苯磺酸钠为丁烯氟虫腈的分散稳定剂。 对制备的微胶囊进行了表征,系统研究了丁烯氟虫腈微胶囊的载药量、包封率、缓释性能和抗光解性能随着组装层数增加的变化规律。 结果表明,组装层数为6~8层的丁烯氟虫腈微胶囊的包封率达到80%以上,达最高释放量所需要的时间为60 h,光解率降到20%以下,综合效果最好。     

Dynamic Release of Propranolol HCl from Cationic Ion–Exchanger–Loaded Calcium Alginate Beads

The dynamic release of drug propranolol HCl from the propranolol HCl–resin complex (PRC) loaded calcium alginate beads has been studied in the buffer media of pH 1.2 at the physiological temperature 37°C. The PRC encapsulated beads demonstrated nearly 58.04% release while naked PRC particles released 98.00% drug in 24 h in the gastric fluid. The amount of drug released was found to increase with and decrease in the amount of sodium alginate in the beads. Similarly, with the increase in the amount of entrapped PRC particles within the beads, the quantity of drug released was also observed to increase. The degree of crosslinking of beads also affected the release kinetics. Interestingly, the release from naked PRC particles followed ‘first‐order’ kinetics while PRC particles, entrapped in calcium–alginate beads, exhibited ‘diffusion controlled’ release behavior as indicated by liner nature of fractional release vs. √t plot.     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Effect of the Addition of Alginate and/or Tetracycline on Brushite Cement Properties

Calcium phosphate cements have the advantage that they can be prepared as a paste that sets in a few minutes and can be easily adapted to the shape of the bone defect, which facilitates its clinical application. In this research, six formulations of brushite (dicalcium phosphate dihydrated) cement were obtained and the effect of the addition of sodium alginate was analyzed, such as its capacity as a tetracycline release system. The samples that contain sodium alginate set in 4 or 5 min and showed a high percentage of injectability (93%). The cements exhibit compression resistance values between 1.6 and 2.6 MPa. The drug was released in a range between 12.6 and 13.2% after 7 days. The antimicrobial activity of all the cements containing antibiotics was proven. All samples reached values of cell viability above 70 percent. We also observed that the addition of the sodium alginate and tetracycline improved the cell viability.     

Alginate/gelatin blend films and their properties for drug controlled release

Films of alginate and gelatin, cross-linked with Ca²⁺, with ciprofloxacin hydrochloride as model drug incorporated in different concentrations, were obtained by a casting/solvent evaporation method. Chemical, morphological and mechanical properties characterization was carried out, as well as the studies of the factors that influence the drug releasing from alginate and gelatin films. These factors included the component ratio of alginate and gelatin, the loaded amount of ciprofloxacin hydrochloride, the pH and ionic strength of the release solution, the thickness of the drug loaded films and the cross-linking time with Ca²⁺ and others. The best values of the tensile strength at 101.5 MPa and breaking elongation at 19.4% of blend films were obtained when the gelatin content was 50 wt.%. The results of controlled release tests showed that the amount of ciprofloxacin hydrochloride released decreased with an increase in the proportion of gelatin present in the film. Moreover, the release rate of drug decreased as the amount of drug loaded in the film increased. The alginate/gelatin films were also sensitive to pH and ionic strength. For pH 7.4 the drug release was faster compared to pH 3.6, being simultaneously accelerated by a higher ionic strength. It was observed that in simulated intestinal fluid, the thickness of the film increased from 30 μm to 55 μm with a concomitant reduction of the ciprofloxacin hydrochloride concentration from 100% to 83.5%. When the cross-linking time of these films in the Ca²⁺ solution were 0 min, 5 min, 15 min and 30 min, the drug release rate attained 100%, 100%, 77.6% and 52.4%, respectively, within 24 h. All the results indicated that the alginate/gelatin film was potentially useful in drug delivery systems.     

pH-Responsive Hydrogel Beads Based on Alginate, κ-Carrageenan and Poloxamer for Enhanced Curcumin,Natural Bioactive Compound,Encapsulation and Controlled Release Efficiency

Polyphenolic compounds are used for treating various diseases due to their antioxidant and anticancer properties. However, utilization of hydrophobic compounds is limited due to their low bioavailability. In order to achieve a greater application of hydrophobic bioactive compounds, hydrogel beads based on biopolymers can be used as carriers for their enhanced incorporation and controlled delivery. In this study, beads based on the biopolymers-κ-carrageenan, sodium alginate and poloxamer 407 were prepared for encapsulation of curcumin. The prepared beads were characterized using IR, SEM, TGA and DSC. The curcumin encapsulation efficiency in the developed beads was 95.74 ± 2.24%. The release kinetics of the curcumin was monitored in systems that simulate the oral delivery (pH 1.2 and 7.4) of curcumin. The drug release profiles of the prepared beads with curcumin indicated that the curcumin release was significantly increased compared with the dissolution of curcumin itself. The cumulative release of curcumin from the beads was achieved within 24 h, with a final release rate of 12.07% (gastric fluid) as well as 81.93% (intestinal fluid). Both the in vitro and in vivo studies showed that new hydrogel beads based on carbohydrates and poloxamer improved curcumin’s bioavailability, and they can be used as powerful carriers for the oral delivery of different hydrophobic nutraceuticals.     

肽类药物口服剂型材料及控制释放性能研究──Ⅱ.含有添加剂的壳聚糖-海藻酸盐微囊对胰岛素的控释作用

应用壳聚糖－海藻酸盐微囊技术制备了一系列含有添加剂的胰岛素微囊,并研究了在添力。剂存在下,不同反应条件对微囊的胰岛素包封率及其释放性能的影响．结果表明,在添加剂存在下,海藻酸钠浓度越高,微囊在胃液中释放率越大,在模拟小肠液中释放速率越低,并且微球的韧性很强,不易破裂;海藻酸钠与添加剂的质量比越大,微囊的包封率越大,胃液中释放率减小;胰岛素含量越高,包封率越小,胃液中释放率越大;明胶和牛血清白蛋白的加入使微囊在胃液中释放率显著增大,微球的强度和韧性大大增强,尤其明胶的加入使微囊在模拟小肠液中释放率显著降低,释放达到最大值的时间延长．     

Pickering emulsions stabilized by hydrophobically modified alginate nanoparticles: Preparation and pH-responsive performance in vitro

pH-responsive Pickering emulsions were prepared, taking the hydrophobic modified calcium alginate nanoparticles (MCA) of pH sensitivity as emulsifiers. The MCAs were obtained via gelation between Ca²⁺ in emulsion and alginate sodium that reacted with diacetone acrylamide since alginate sodium was too hydrophilic to be used as a stabilizer. The effect of MCA characteristics, Ca²⁺ content, and pH on the preparation and property of emulsion was evaluated. Then, the released behaviors of MCA-stabilized emulsion loading oil-soluble drug of curcumin were investigated in vitro. The results demonstrated that Pickering emulsions released curcumin intestine-specifically (37% in 4 hours with a pH of 6.8), compared with the one in the gastric fluid (3% in 4 hours with a pH of 1.5), proving that MCA had similar pH sensitivity to alginates and probably as the promising candidate in oral drug controllable release.     

Multiparticulate chitosan-dispersed system for drug delivery

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.