Double-walled microspheres loaded with meglumine antimoniate: preparation,characterization and in vitro release study

Objective: The objective of this study was to fabricate double-walled poly(lactide-co-glycolide) (PLGA) microspheres to increase encapsulation efficiency and avoid rapid release of hydrophilic drugs such as meglumine antimoniate.

Methods: In this study, double-walled and one-layered microspheres of PLGA were prepared using the emulsion solvent evaporation technique to better control the release of a hydrophilic drug, meglumine antimoniate (Glucantime®), which is the first choice treatment of cutaneous leishmaniasis. The effect of hydrophobic coating on microspheres' size, morphology, encapsulation efficiency and drug release characteristics was evaluated. Furthermore, the presence of antimony in meglumine antimoniate made it possible to observe the drug distribution within the microspheres' cross section by means of energy dispersive X-ray spectroscopy.

Results: Drug distribution images confirmed accumulation of the drug within the inner core of double-walled microspheres. In addition, these microspheres encapsulated the drug more efficiently up to 87% and demonstrated reduced initial burst and prolonged release compared to one-layered microspheres. These superiorities make double-walled microspheres an optimum candidate for sustained delivery of hydrophilic drugs.

Conclusion: Double-walled microspheres provide some advantages over traditional microspheres overcoming most of their limitations. Double-walled microspheres were found to be more efficient than their corresponding one-layered microspheres in terms of encapsulation efficiencies and release characteristics.     

5-氟尿嘧啶载药微球的制备工艺及性能研究

以PLA为载体材料,以5-Fu为模型药物,制备5-Fu/PLA载药微球,通过正交设计优化微球制备工艺.另外,检测了载药微球的回收率、稳定性、缓释性能等物理性质.用紫外分光光度计测定药物含量,激光粒度仪分析粒径. 结果表明,载药微球的平均粒径为(133.2±32.5)nm,平均包封率为(11.3±5.0)%,缓释时间延长至80～100h,具有良好的缓释功能.     

Development and characterization of wheat gluten microspheres for use in a controlled release system

The purpose of this study was the development and characterization of wheat gluten microspheres for use as controlled release devices, and the evaluation of the effect of the addition of poly (ethylene glycol) (PEG). Diltiazem hydrochloride was used as the model drug in the in vitro release essay. The physical–chemical and morphological properties of the microspheres were evaluated, as well as their encapsulation efficiency. Porosity varied with the presence or absence of PEG. The diltiazem encapsulation efficiency was 72.8% and 96.7% for wheat gluten and gluten/PEG 95/05 microspheres, respectively. The DSC and FTIR results indicated interactions between the microparticles and additives used. In the in vitro release tests it was observed that, for all the studied systems, the burst effect occurred in the first 2 h of release and the microspheres prepared with PEG had a faster release rate. In the attempt to elucidate the release mechanism, the systems were treated based on two well known mathematical models: the Higuchi and the power law. It was found that the microsphere release mechanism is not exclusively diffusion-controlled and, probably, the release occurs through a combination of partial diffusion through the swelling matrix and hydrophilic pores.     

Controlled release system for ametryn using polymer microspheres: preparation, characterization and release kinetics in water

The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92±0.74 μm and 5.63±0.68 μm, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative.     

Encapsulation of nitrogen fertilizers in mixtures with organoclays for controlled release

Clean Technologies and Environmental Policy - To increase the effectiveness of fertilizers, new controlled release nitrogen fertilizers have been developed from a mixture of urea and natural...     

Formulation and in vitro characterization of long-acting PLGA injectable microspheres encapsulating a peptide analog of LHRH

The present study aimed to formulate triptorelin acetate(TA)into poly(D,L-lactic-co-glycolic)acid(PLGA)based injectable sustained-release microspheres(TA-PLGA-MS)by usingdouble emulsion solvent extraction/evaporation(DESE)technique and investigate the effects of various material attributes and process parameters on the quality attributes such as size,shape,surface morphology,encapsulation efficiency(EE)and in vitro release behavior of these microspheres.Variable compositions of the outer water phase,type of the organic solvents,volume ratios of inner water phase to oil phase,PLGA concentrations,and the powers for emulsification in the preparation of the microspheres showed an influence on their quality attributes.An optimal formulation(F-2)obtained from this univariate approach possess an excellent EE value of 63.5%±3.4%and an average volumetric particle size of 35.3±1.8μm.This formulation was further accomplished with different solidification rates assisted by variable incubation temperatures,which exhibited an impact on the shape/surface and inner morphology of the microspheres.The resultant microspheres also displayed different in vitro release patterns.The matrices processed with a high incubation temperature conferred the fastest and the most complete drug release profile over the period of 63 days.Thus,the solidification rate could be identified as one of the critical process parameters that affected the quality of the PLGA based injectable microspheres specifically designed for the prolonged delivery of TA.     

Preparation and characterization of collagen microspheres for sustained release of VEGF

In this study, we prepared injectable collagen microspheres for the sustained delivery of recombinant human vascular endothelial growth factor (rhVEGF) for tissue engineering. Collagen solution was formed into microspheres under a water-in-oil emulsion condition, followed by crosslinking with water-soluble carbodiimide. Various sizes of collagen microspheres in the range of 1–30 μm diameters could be obtained by controlling the surfactant concentration and rotating speed of the emulsified mixture. Particle size proportionally decreased with increasing the rotating speed (1.8 μm per 100 rpm increase in the range of 300–1,200 rpm) and surfactant concentration (3.1 μm per 0.1% increase in the range of 0.1–0.5%). The collagen microspheres showed a slight positive charge of 8.86 and 3.15 mV in phosphate-buffered saline and culture medium, respectively. Release study showed the sustained release of rhVEGF for 4 weeks. Released rhVEGF was able to induce capillary formation of human umbilical vein endothelial cells, indicating the maintenance of rhVEGF bioactivity after release. In conclusion, the results suggest that the collagen microspheres have potential for sustained release of rhVEGF.     

纳米金刚石/酵母-壳聚糖复合微球的制备及光热控释性能

开发高性能功能性光热凝胶并建立药物控释模型对农药智能输送材料的开发具有重要意义。以酵母-壳聚糖水凝胶(YS-CS)为基体,引入光热材料纳米金刚石(DND),通过碱凝胶法合成了纳米金刚石/酵母-壳聚糖(DND/YS-CS)交联网络结构复合凝胶微球,研究了复合微球的微观结构、力学性能和光热转换性能;以吲哚丁酸(IBA)为模型药物,探讨DND/YS-CS对IBA的负载性能和控释性能,揭示复合微球对IBA的光热控释机制。结果表明：复合微球具有良好的力学性能,在分别超声和离心1 h后,DND含量为2.0 mg/mL复合微球保水能力分别达到70.5%和74%;复合微球具有良好的光热转换能力,一个太阳光强度下,最高温度可达37.6℃;DND含量为1.2 mg/mL复合微球对IBA的吸附量最高,可达到41.73μg/mg;微球在光下药物释放模式符合Korsmeyer-Peppas模型,在光下具有明显的刺激响应行为,药物释放呈现“开-关”模式。通过控制光的照射强度控制药物释放,在农业领域有广阔的应用前景。     

Dynamics of controlled release of heparin from swellable crosslinked starch microspheres

The microspheres of crosslinked starch have been prepared and characterized by IR spectral analysis and SEM technique. The prepared microspheres were loaded with an anticoagulant drug ‘heparin’ and the kinetics of in-vitro release of heparin was investigated spectrophotometrically at physiological pH (7.4) and body temperature (37 °C). The influence of percent loading of heparin, chemical architecture of the microspheres and pH of the release medium were examined on the release profiles of the drug. The chemical stability of heparin was tested in phosphate buffer saline (pH 7.4) and the release was also studied in various simulated biological fluids.     

负载型高铁酸盐缓释剂的缓释效果研究

采用缓（控）释放技术,利用硅藻土、氧化铝、分子筛三种吸附剂来负载高铁酸盐,制成了负载型高铁酸盐缓释剂,并通过条件优化试验,确定出了负载高铁的最佳吸附材料、吸附剂的最佳干燥方式以及最佳负载时间和最佳负载浓度,得到了高铁在一定时间内能缓慢释放,以进行缓释消毒的条件。实验结果表明,负载型高铁酸盐缓释剂具有较高的高铁溶出浓度与持续时间,这一结果为负载型高铁酸盐缓释剂应用于实际水消毒提供了依据。     

Fabrication,characterization and long-term in vitro release of hydrophilic drug using PHBV/HA composite microspheres

In this paper, we fabricated polyhydroxybutyrate-co-hydroxyvalerate (PHBV)/Hydroxyapatite (HA) composite microspheres as a long-term drug delivery system. The characterization and in vitro release properties of the system were investigated. It was observed that the PHBV/HA composite microspheres showed very low initial burst that could be neglected, owing to the high affinity and absorbability of nano-HA particles, and the sustained release lasted more than 10 weeks. The in vitro release rate was controlled by diffusion rate of drugs from polymer matrices, and the release profile can be expressed by the Higuchi equation. From our work, it indicated that PHBV/HA composite microsphere could be a promising long-term drug release system.     

Synthesis and characterization of paclitaxel-imprinted nanoparticles for recognition and controlled release of an anticancer drug

Imprinted nanoparticles as drug delivery carriers have been considered because owing to their cross-linked network, they act as the drug reservoir for controlled release. In this study, selective MIPs nanoparticles of paclitaxel (PTX) were successfully developed for application in the biological molecular recognition and in the design of new anticancer drug delivery systems. The MIPs nanoparticles prepared by miniemulsion polymerization technique using methacrylic acid (MAA) and methyl methacrylate as non-covalent functional monomer, ethylene glycol dimethacrylate and trimethylolpropane trimethacrylate (TRIM) as cross-linker agent, azobisisobutyronitrile as initiator, and hexadecane as hydrophobic agent. In order to prepare of MIP nanoparticles, the synthesis conditions and effective parameters, such as: cross-linker agent, different molar ratios of template–functional monomer–cross-linker agent, were investigated. In addition, the effect of different molar ratios of template and monomers on polymers binding and morphology were characterized. Structure and thermal properties of MIPs were confirmed by FT-IR spectroscopy and thermogravimetric analysis. Imprinted nanoparticles showed significant drug loading and encapsulation efficiency, 17.8 and 100 %, respectively. The particle size of MIP nanoparticles varies between 187 and 726 nm, according the SEM images and laser light scattering data. The imprinted nanoparticles showed satisfactory affinity (84 %) to PTX with a binding of 12 times higher than non-imprinted nanoparticles in biological samples when MAA and TRIM were used as functional and cross-linker monomer, respectively. Results from release experiments of MIPs showed a very slow and controlled release of PTX which would be helpful for sustained drug delivery.     

Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release

Hollow hydroxyapatite (HA) microspheres were fabricated by a simple spray drying method in this study. Moreover, the dissolution behavior of these hollow HA microspheres after immersion in simulated body fluid (SBF) was also studied. The results indicated that the dissolution of the HA microspheres in SBF is not homogeneous in a layer-by-layer fashion but was preferential at different locations of the particle surface. Generically, dissolution preferentially occurs on the location with looser structure and high porosity of the microspheres. The degradable HA microspheres are expected to have potential applications in bone local drug delivery systems.     

硅烷偶联剂对碳微球的表面化学修饰

首先采用混酸体系对碳微球(CMSs)表面进行氧化处理,使CMSs表面引入含氧官能团,进而以γ-(甲基丙烯酰氧)丙基三甲氧基硅烷(KH-570)与CMSs表面发生缩合反应,得到了表面有机修饰的CMSs.利用傅立叶红外光谱仪、场发射扫描电子显微镜、X射线光电子能谱等检测手段对各阶段的产物进行了形貌和结构表征,并研究了其在乙...     

包覆型高铁酸钾缓释剂的制备及性能表征

以切片石蜡为包覆壁材,以高铁酸钾为芯材,采用熔化悬浮冷凝法制得包覆型高铁酸钾。实验结果表明：分散方式对包覆率的影响很大,当搅拌速度为800r／min,超声时间为30min时,包覆率可达到85.5％;采用红外光谱、X射线衍射和扫描电镜对包覆后的产品进行了性能表征,结果发现,切片石蜡对高铁酸钾的包覆并没有破坏高铁酸钾的组分活性,包覆后高铁酸钾的缓释符合Q=kt^n动力学模型,而且持续缓释性能良好,切片石蜡与高铁酸钾质量比为3：1、5：1和10：1的包覆产品的理论缓释半衰期分别可达到7.5天、2.6月和17.0年。     

Sustained release microspheres of diclofenac sodium using PEGylated rosin derivatives

The PEGylated derivatives of rosin-PD-1 and PD-2 synthesized and characterized earlier (Nande et al., 2006) were investigated as potential materials for sustained release microsphere prepared by emulsion solvent evaporation method using diclofenac sodium (DCS) as model drug. All the microspheres exhibited smooth surfaces intercepted by pores; their sizes (d(90)) ranged between 11-24 microm. The entrapment efficiency (< 80%) of the microspheres increased proportionally with derivative concentration. Presence of solvent like isopropyl alcohol or dichloromethane rendered the microspheres with large sizes but with reduced drug entrapment. Microspheres with small size were obtained at an optimum viscosity of liquid paraffin; any change lead to increase in the particle size. Magnesium stearate was found to be most suitable detackifier in the present system. The drug release was directly related to the particle size--small sized microspheres released drug at a faster rate. The dissolution data complied with Higuchi equation while the mechanism of drug release was Fickian diffusion (n approximately 0.5). Controlled inhibition of edema, as tested by hind paw edema method, was observed for 10 h when the microspheres were administered intraperitoneally. The present study found the derivatives as promising materials for preparing microspheres for sustained delivery of DCS.     

Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150–250?µm) or a large pore size (LPC; 250–350?µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58?±?2.8, 53?±?1.9, and 50?±?2.1?N, respectively. The measured porosity values were 41.2?±?1.53, 65.2?±?1.1, and 60.7?±?1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40?days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.     

A single-step synthesis of gold nanochains using an amino acid as a capping agent and characterization of their optical properties

We demonstrated a simple single-step synthesis of gold nanochains by reducing aqueous chloroaurate ions (AuCl(4)(-)) with sodiumborohydride (NaBH(4)) in the presence of an amino acid (glutamic acid and histidine) as a stabilizer. The structure and optical properties of gold nanochains and nanowires were characterized by transmission electron microscopy, UV-visible spectroscopy, infrared spectroscopy and femtosecond z-scan measurements. The results suggested that the gold nanochains and nanowires were formed via the nanospheres fusing into one another by an oriented attachment mechanism through dipole-dipole interactions. The z-scan measurements on Au nanowires showed a transition from saturable absorption to reverse saturable absorption as the pump intensity increased.     

Synthesis of titania microspheres with hierarchical structures and high photocatalytic activity by using nonanoic acid as the structure-directing agent

The titania, as the heterogeneous photocatalyst, has attracted much attention in attempts to eliminate pollutants, especially organic compounds in water and air. In this study, the titania microspheres with hierarchical structures were prepared by a combined sol–gel and solvothermal method. The X-ray powder diffraction (XRD) result indicated that the synthesized titania microspheres were of anatase phase. Field-emission scanning electron microscope (FESEM) and high-resolution transmission electron microscope (HRTEM) showed that the microspheres with well-dispersity had an average diameter of 651 nm and were composed of nanoparticles with about 20 nm in diameter. The Brunauer–Emmett–Teller (BET) results showed that the microspheres possessed high surface areas and lots of mesopores. Further study indicated that the synthesized titania microspheres exhibited high photocatalytic activity and had an important advantage over the commercial P25.     

Preparation and characterization of gold nanoparticles using ascorbic acid as reducing agent in reverse micelles

In this study, well-dispersed gold nanoparticles were prepared by the reduction of HAuCl₄ in sodium bis(2-ethylhexyl)sulfosuccinate/isooctane reverse micelles system using ascorbic acid as reducing agent. The properties of the obtained nanoparticles were characterized with transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, and UV–vis absorption spectrophotometer. Due to its high water solubility, biodegradability, and low toxicity, ascorbic acid could be used as a benign naturally available reducing agent to synthesize gold nanoparticles.