Clonazepam release from core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) triblock copolymers

The triblock copolymer based on poly(-caprolactone) (PCL) as hydrophobic part and poly(ethylene glycol) (PEG) as hydrophilic one was synthesized and characterized. Core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) (CEC) block copolymer were prepared by a dialysis technique. According to the amphiphilic characters, CEC block copolymer can self-associate at certain concentration and their critical association concentration (CAC) was determined by fluorescence probe technique. CAC value of the CEC-2 block copolymer was evaluated as 0.0030 g/l. CAC values of CEC block copolymer decreased with the increase of PCL chain length, i.e. the shorter the PCL chain length, the higher the CAC values. From the observation of transmission electron microscopy (TEM), the morphologies of CEC-2 core-shell type nanoparticles were spherical shapes. Particle size of CEC-2 nanoparticles was 32.3±17.3 nm as a monomodal and narrow distribution. Particle size, drug loading, and drug release rate of CEC-2 nanoparticles were changed by the initial solvents and the molecular weight of CEC. The degradation behavior of CEC-2 nanoparticles was observed by ¹H NMR spectroscopy. It was suggested that clonazepam (CNZ) release kinetics were dominantly governed by diffusion mechanism.     

5-Fu/PLGA 微球的制备

以可生物降解高分子材料乳酸—羟乙酸共聚物(PLGA)为载体,以5—氟脲嘧啶(5-Fu)为活性药物,用相分离—凝聚法制备了可供肿瘤动脉栓塞化疗用微球,并进行了初步的微球体外药物释放试验。     

Doxorubicin release from core-shell type nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by 1H nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around 50 nm approximately 300 nm according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. 1H-NMR spectroscopy using D2O and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.     

Drug release from core-shell type nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran

This study prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran. The synthesis of the PLGA-dextran conjugate was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. The PLGA grafted-dextran was able to form nanoparticles in water by self-assembly and their particle size was 245.3?±?95.1?nm. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values were determined from the fluorescence excitation spectra and were found to be 0.006?g?l^?1. Morphological observations using a scanning electron microscope (SEM) showed that the polymeric nanoparticles of the PLGA-dextran conjugate have uniformly spherical shapes. Their size and morphology provide them with acceptable properties for use as a drug-targeting carriers. Drug release from core-shell type nanoparticles was faster in the presence of dextranase, indicating that core-shell type nanoparticles of PLGA grafted-dextran can be used as an oral drug carriers.     

Sustained release of ganciclovir from poly(lactide-co-glycolide) microspheres

Biodegradable poly(lactide-co-glycolide) microspheres loaded with ganciclovir were produced using the emulsification/solvent evaporation technique. The effects of drug-to-polymer ratio and dispersion time on the drug content in the microspheres were investigated. The release rate of the drug was studied for 20 weeks in a phosphate buffered solution of pH 7 at 37°C. Data revealed that lower drug content was obtained with increasing drug-to-polymer ratio and decreasing dispersion time. The release of the drug followed a triphasic release pattern, i.e. an initial burst, a diffusive phase and a second burst. The initial burst occurred within the first 2 days of immersion. After the burst, the release was by diffusion for up to 13 weeks, followed by another burst release, which signals the onset of bulk degradation of the polymer. Gel permeation chromatography (GPC), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and ultraviolet spectroscopy (UV) were used to follow the hydrolytic degradation and drug release rate of the microspheres.     

Controlled release of dexamethasone from poly(vinyl alcohol) hydrogel

This study investigated a chemically crosslinked poly(vinyl alcohol) (PVA) hydrogel controlled drug delivery system to deliver the anti-inflammatory drug dexamethasone (DEX). The PVA hydrogels, with different crosslinking densities, were characterized by swelling studies, electron scanning microscopy, viscosity, Fourier transform infrared spectroscopy (FTIR) and in vitro release assessment. Increasing crosslinking density slowed and decreased swelling and water absorption. FTIR analysis suggested DEX has possible interactions with the crosslinker and the PVA polymer. In vitro release of DEX from PVA hydrogels was sustained for 33 days and appeared to fit the Higuchi and Korsmeyer–Peppas models. This work indicates the likelihood of PVA hydrogel as a controlled drug release system for DEX for anti-inflammatory uses.     

Drug release from core-shell type nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran

This study prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran. The synthesis of the PLGA-dextran conjugate was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. The PLGA grafted-dextran was able to form nanoparticles in water by self-assembly and their particle size was 245.3 +/- 95.1 nm. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values were determined from the fluorescence excitation spectra and were found to be 0.006 g l(-1). Morphological observations using a scanning electron microscope (SEM) showed that the polymeric nanoparticles of the PLGA-dextran conjugate have uniformly spherical shapes. Their size and morphology provide them with acceptable properties for use as a drug-targeting carriers. Drug release from core-shell type nanoparticles was faster in the presence of dextranase, indicating that core-shell type nanoparticles of PLGA grafted-dextran can be used as an oral drug carriers.     

超氧化物歧化酶乳酸-羟乙酸共聚物微球的制备及其性质

利用复乳溶剂挥发法制备了超氧化物歧化酶（SOD）的乳酸－羟乙酸共聚物（PLGA）微球，考察了各工艺因素对微球粒径、包封率等的影响，通过扫描电子显微镜（SEM）、差示扫描量热分析（DSC）初步研究了其性质，结果表明，通过调整内水相的体积及浓度，分散相体积及PH值，可得到较高包封率，粒径在20－30μm，形态圆整，表面多孔的SOD微球，DSC表明SOD被有效地包入了PLGA微球中。     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

聚(DL-乳酸-羟基乙酸)共聚物75/25中有机溶剂残留量的GC测定

目的:测定聚(DL-乳酸-羟基乙酸)共聚物75／25中乙酸乙酯、二氯甲烷、乙醇的含量。方法:采用毛细管气相色谱法,色谱系统为:AC20色谱柱;柱温40℃;载气为氮气;检测器为FID;外标法计算含量。结果:在色谱条件下,测得各有机溶剂线性良好(r>0．99);平均回收率为99．3％～99．7％;RSD在0．15％～0．96％;最低检测限0．245～2．520μg·mL-1,3批样品中3种有机溶剂残留量符合要求。结论:该方法灵敏、准确、可靠。     

Slow release of two antibiotics of veterinary interest from PVA hydrogels

Two antibiotics, tylosin tartrate and oxytetracycline hydrochloride, were entrapped in poly(vinyl alcohol) (PVA) hydrogels (MW 31,000-50,000) by a cryogen procedure obtaining a controlled release system suitable for veterinary application. It was found that at a low drug matrix loading (10 mg/ml), the in vitro release rate of both antibiotics could be reduced by a previous freeze drying of the gel, while no reduction in drug rate took place in heavily loaded matrices (300 mg/ml). When PVA hydrogels containing tylosin were administered to rats per os the drug could not be detected in the blood, but it was found in organs,: liver, kidneys, and muscles, for up to 120 h. On the other hand, when the same amount of drug was administered orally as powder, no appreciable organ accumulation was detected, while the drug was found in faeces and urine. These data show that PVA hydrogels can be a suitable slow release system for tylosin administration. Oxytetracycline could also be quantitatively entrapped and released from PVA hydrogels, but once administered per os to rats, it was not detected in blood or organs.     

60Co辐照对睾丸酮/乳酸-乙醇酸共聚物微球理化特性及体外释放的影响

目的 :睾丸酮 (T) /乳酸 -乙醇酸共聚物 (PLGA)微球6 0 Co辐照灭菌可行性研究。方法 :T/PLGA微球在6 0 Co源下 ,以 2 5kGy的剂量进行辐照 ,对微球辐照前后主药T、载体PLGA的理化特性和微球体外释药速率的变化进行比较 ,考察6 0 Co辐照对T/PLGA微球理化特性及药物体外释放的影响。结果 :6 0 Co辐照引起PLGA分子量一定程度的下降 ,但对T/PLGA微球的理化特性及体外释药速率没有影响。结论 :初步的可行性研究表明T/PLGA微球可用6 0 Co辐照灭菌     

Novel approach for delivery of insulin loaded poly(lactide-co-glycolide) nanoparticles using a combination of stabilizers

Insulin stability during microencapsulation and subsequent release is essential for retaining its biological activity. The successful delivery of insulin relies on the proper selection of stabilizers in addition to other parameters. Attempts were made to address the problem with a few combination of stabilizers for maintaining the integrity of insulin during formulation and delivery. Insulin loaded nanoparticles with different stabilizers such as pluronic F68, trehalose, and sodium bicarbonate were prepared by the double emulsion evaporation method using two different copolymer ratios of poly(DL-lactide-co-glycolide) (50:50 and 85:15). The presence of stabilizers in the nanoparticles resulted in an increase in the particle size but a reduction of encapsulation efficiency. Insulin release rate was comparatively higher for the batches containing stabilizers when compared with controls for both the copolymer ratios. Also the presence of stabilizers resulted in sustained release of insulin resulting in prolonged reduction of blood glucose levels in streptozotocin induced diabetic rats. From the in vitro and in vivo studies, we concluded that a combination of stabilizers results in beneficial effects without compromising the advantages of delivery systems.     

Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-Fluorouracil delivery systems for active targeting

In this article, a reproducible emulsion polymerization process is described to prepare core/shell colloidal nanospheres, loaded with 5-Fluorouracil, and consisting of a magnetic core (magnetite) and a biodegradable polymeric shell [poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate), or poly(octylcyanoacrylate)]. The heterogeneous structure of these carriers can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing an active drug targeting without a concurrent systemic distribution. Zeta potential determinations as a function of ionic strength showed that the surface behaviour of the core/shell particles is similar to that of pure cyanoacrylate particles. The first magnetization curve of both magnetite and magnetite/polymer particles demonstrated that the polymer shell reduces the magnetic responsiveness of the particles, but keeps unchanged their ferrimagnetic character. Two drug loading mechanisms were studied: absorption or entrapment in the polymeric network, and surface adsorption. We found that the acidity of the medium had significant effects on the drug absorption per unit mass of polymer, and needs to be controlled to avoid formation of macroaggregates and to reach significant 5-Fluorouracil absorption. The type of polymer and the drug concentration are also main factors determining the drug incorporation to the core/shell particles. 5-Fluorouracil release evaluations showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.     

Characteristic and controlled release of anticancer drug loaded poly (D,L-lactide) microparticles prepared by spray drying technique

Anticancer drug release from polylactic acid microspheres prepared by the spray-drying process was studied. Several process parameters and properties of the polymer solution have been investigated. Normal size distributions with diameters ranging from 5-10 #119 m were obtained by the spray drying technique. The yield of microspheres recovered depended on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50%, and the experimental drug loading approached the theoretical drug loading. Scanning electron microscopy indicated that microspheres were composed of a dense thin skin layer and porous core. The magnitude of this effect depended on the inlet temperature, feed polymer concentration and airflow rate. Increasing inlet temperature and polymer concentration resulted in an intact particle shape and a slower drug dissolution rate. The in-vitro release of anticancer drug from microspheres was sustained over 7 days. The drug release behaviour depended on inlet temperature, air flow rate, PLA concentration and drug loading. The anticancer drug release rate from polylactic acid microspheres prepared by the spray-drying method was depressed, and the long-acting release could be achieved by appropriate operating parameters.     

Novel,dynamic on-line analytical separation system for dissolution of drugs from poly(lactic acid) nanoparticles

A novel method for investigating drug release in a dynamic manner from nanoparticles including, but not limited to, biodegradable poly(lactic acid) (PLA) is reported. The PLA nanoparticles were prepared by the nanoprecipitation method. Two poorly soluble drugs, beclomethasone dipropionate (BDP) and indomethacin, were encapsulated into PLA nanoparticles, and their dissolution from the nanoparticles were followed in a dynamic way. The on-line method comprised a short column (vessel) packed with the PLA nanoparticles, on-line connected to an analytical liquid chromatographic column via a multiport switching valve equipped with two loops. The system allowed monitoring of the drug release profiles in real time, and the conditions for the drug release could be precisely controlled and easily changed. The effects of solvent composition and temperature on the rate of dissolution of the drugs from the PLA nanoparticles were investigated. The system proved to be linear for the drugs tested over the concentration range 10–3000 ng (n = 6, R² = 0.999 and 0.997 for indomethacin and beclomethasone, respectively) and repeatable (RSD of peak areas <0.5%). The recoveries of the dissolution study were quantitative (120 and 103% for indomethacin and beclomethasone, respectively).     

Colchicine encapsulation within poly(ethylene glycol)-coated poly(lactic acid)/poly(epsilon-caprolactone) microspheres-controlled release studies

Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local delivery of agents capable of modulating vascular responses have the potential to prevent restenosis. However, the development of injectable microspheres for maintaining high tissue levels of drugs at the site of vascular injury is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, colchicine, in polyethylene glycol (PEG)-coated biodegradable microspheres composed of poly(lactic acid)/poly(epsilon-caprolactone) blends, with a mean diameter of 3-6 microm. A solution of colchicine and blends of polylactic acid (PLA)/polycaprolactone (PCL) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of PEG (or polyvinyl alcohol) with stirring by a high-speed homogenizer to form microspheres. Colchicine recovery in microspheres ranged from 30-50% depending on the emulsification system and the ratio of polymer blends used for the preparations. Scanning electron microscopy revealed that the PLA/PCL microspheres were spherical in shape and had a smooth surface texture. Results of in vitro release studies showed that it is possible to control the colchicine release by choosing the appropriate particle size, loading, and PLA/PCL composition. Water permeability through the PLA membrane was greater, when compared with PCL blends. The amount of drug release also was much higher (58.3%) in PLA compared with PCL (39.3%) microspheres, for 30 days. Therefore, we concluded that the drug release from the microspheres followed a diffusion mechanism where bulk erosion and surface deposition were negligible. These PEG-coated PLA/PCL microspheres may have potential for targeting antiproliferative agents for prolonged periods to treat restenosis.     

Clonazepam release from core-shell type nanoparticles of poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) triblock copolymers

The triblock copolymer based on poly(epsilon-caprolactone) (PCL) as hydrophobic part and poly(ethylene glycol) (PEG) as hydrophilic one was synthesized and characterized. Core-shell type nanoparticles of poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) (CEC) block copolymer were prepared by a dialysis technique. According to the amphiphilic characters, CEC block copolymer can self-associate at certain concentration and their critical association concentration (CAC) was determined by fluorescence probe technique. CAC value of the CEC-2 block copolymer was evaluated as 0.0030 g/l. CAC values of CEC block copolymer decreased with the increase of PCL chain length, i.e. the shorter the PCL chain length, the higher the CAC values. From the observation of transmission electron microscopy (TEM), the morphologies of CEC-2 core-shell type nanoparticles were spherical shapes. Particle size of CEC-2 nanoparticles was 32.3+/-17.3 nm as a monomodal and narrow distribution. Particle size, drug loading, and drug release rate of CEC-2 nanoparticles were changed by the initial solvents and the molecular weight of CEC. The degradation behavior of CEC-2 nanoparticles was observed by 1H NMR spectroscopy. It was suggested that clonazepam (CNZ) release kinetics were dominantly governed by diffusion mechanism.     

Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers

In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.