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1.
聚乙二醇-聚乳酸嵌段共聚物在药物递送系统中的应用 总被引:1,自引:0,他引:1
聚乙二醇-聚乳酸嵌段共聚物具备良好的生物相容性和生物可降解性,是良好的纳米级药物载体。嵌段共聚物具有载药能力强、粒径小、体内循环时间长、主动靶向性和被动靶向性等特点,因此在药物递送系统中得到广泛应用。简要介绍了聚乙二醇-聚乳酸嵌段共聚物的合成和性质,及其作为脂质体、胶束、微球等载体在药物递送系统中的最新进展。 相似文献
2.
In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content
of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic
model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence
of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The
resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology,
total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical
properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used
in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer
content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to
polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts
of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio
of TEC. 相似文献
3.
聚乳酸乙醇酸共聚物(PLGA)是一种可生物降解的高分子聚合物,具有良好的生物相容性,其降解产物为乳酸和乙醇酸,是机体正常代谢的中间产物,最终可分解为二氧化碳和水,并分别经肺和肾脏排出体外,对人体不产生危害,所以PLGA在微球制剂的制备中常作为首选载体。近年来PLGA微球制剂在医药领域有着飞跃发展,尤其是在抗肿瘤、免疫疫苗、蛋白给药、基因治疗、诊断试剂和细胞支架等方面显现出很大优势。而且已有许多PLGA微球获得美国FDA批准上市,临床应用也有令人满意的效果,未见报道有严重的不良反应。但现阶段国内生产的PLGA缓释微球的质量还有很多不足之处如微球粒径偏大、包封率和载药量偏低、突释过大等,有待进一步提高和改进。本文将综述在制备包裹水溶性药物的PLGA微球过程中相关因素如药物本身理化性质、制备方法、PLGA结构特点、有机溶剂等对微球粒径、包封率的影响,以期为提高以PLGA为药物载体的药效奠定良好的理论基础。 相似文献
4.
J Marchand P Varcin D Riochet P Montagne M L Cuilliere J Duheille B Pau 《Biopolymers》1992,32(8):971-980
To optimize antigen-antibody reactions, we have synthesized chemically well-defined hydrophilic microspheres. Proteins or haptens were covalently linked to these carriers. When the microsphere conjugates were agglutinated by the corresponding antiserum, the size of the complex artificially increased during the immunological reaction. After optimizing various parameters such as the hydrophilic character, repulsion charges, and amount of antigen coupled to the microspheres, we developed a rapid and sensitive immunoassay based on laser light scattering by the complexes. 相似文献
5.
An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting
of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and
pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation
and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio
1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation.
Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1).
Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size
distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF).
The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of
2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized
formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium,
the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation
that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU.
Published: February 16, 2007 相似文献
6.
In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique
is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose,
poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures
above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during
preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied.
As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing
the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release
rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low
drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres
from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from
matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release
was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted
in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles
of naltrexone can be achieved using a PLA microparticulate system or matrix devices. 相似文献
7.
The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment
of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and
by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique
to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology,
size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated
microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged
from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug
release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions
of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit
S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram,
and in vitro drug release after storage at 40°C/75% relative humidity for 6 months. 相似文献
8.
Conclusion In this study, we found that both heating temperature and heating time affect mean particle size, particle size distribution,
and drug entrapment efficiency of albumin microspheres. The change in heating temperature may affect the particle size of
the product, especially when heating is carried out at a lower temperature (90°C–120°C). Hence the temperature should be selected
on the basis of desired size range. Given that it is desirable for a maximum amount of the drug used in the preparation to
become entrapped in microspheres, heating temperature and heating time for denaturation of albumin should be selected cautiously,
as both have a significant effect on drug entrapment efficiency. In the present case, the highest entrapment was found in
batches prepared by heating at 90°C for 5 minutes. However, the extent of stabilization at the selected temperature and the
time of heating should also be taken into consideration, as they may affect the release of drugs to target tissue. 相似文献
9.
The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres
designed for the subcutaneous release of carboplatin, a chemotherapeutic drug. Poly(D,L-lactide) (PDLLA) microspheres were
prepared by an emulsification/spray-drying method, using the drug-to-polymer weight ratios 1∶9 and 1∶5; blank microspheres
(1% w/v) were prepared as a comparison. Microparticles were characterized in terms of morphology, encapsulation efficiency,
and in vitro drug release behavior. In vivo tests were conducted on rats by subcutaneous injection of microsphere aqueous
suspensions. Levels of carboplatin were evaluated both in the skin and in serum. The microparticles obtained had a spherical
shape; particle size ranged from 5 to 7 μm, dependent on drug loading. Microspheres were able to control the in vitro release
of the drug: approximately 90% to 100% of the carboplatin was released over 30 days. In vivo results showed that the microspheres
were able to release high drug amounts locally, and sustained serum levels of drug were also achieved. Based on these results,
carboplatin-loaded PDLLA microspheres may be useful for local delivery of the antineoplastic drug to the tumor, avoiding tumor
recurrence in small animals, and may decrease the formation of distant metastases.
Published: September 20, 2005 相似文献
10.
The objective of the present study was to optimize the concentration of a chitosan solution, stirring speed, and concentration of drugs having different aqueous solubility for the formulation of chitosan microspheres. Chitosan microspheres (unloaded and drug loaded) were prepared by the chemical denaturation method and were subjected to measurement of morphology, mean particle size, particle size distribution, percentage drug entrapment (PDE), drug loading, and drug release (in vitro). Morphology of the microspheres was dependent on the level of independent process parameters. While mean particle size of unloaded microspheres was found to undergo significant change with each increase in concentration of chitosan solution, the stirring rate was found to have a significant effect only at the lower level (ie, 2000 to 3000 rpm). Of importance, spherical unloaded microspheres were also obtained with a chitosan solution of concentration less than 1 mg/mL. Segregated unloaded microspheres with particle size in the range of 7 to 15 microm and mean particle size of 12.68 microm were obtained in the batch prepared by using a chitosan solution of 2 mg/mL concentration and stirring speed of 3000 rpm. The highest drug load ( microg drug/mg microspheres) was 50.63 and 13.84 for microspheres containing 5-fluorouracil and methotrexate, respectively. While the release of 5-fluorouracil followed Higuchi's square-root model, methotrexate released more slowly with a combination of first-order kinetics and Higuchi's square-root model. The formation of chitosan microspheres is helped by the use of differential stirring. While an increase in the concentration of water-soluble drug may help to increase PDE and drug load over a large concentration range, the effect is limited in case of water-insoluble drugs. 相似文献
11.
Synthesis and characterization of hydroxyapatite-ciprofloxacin delivery systems by precipitation and spray drying technique 总被引:1,自引:0,他引:1
This investigation synthesized and characterized hydroxyapatite (HAP) microspheres, agglomerated microspheres, and implants
containing ciprofloxacin. This delivery system is to be used as an implantable drug delivery system for the treatment of bone
infections. The HAP microspheres were made by chemical precipitation followed by a spray-drying technique. Agglomerated microspheres
were prepared by a wet granulation process using a granulator. Implants were prepared by direct compression of the granules
on a Carver press. Ciprofloxacin was analyzed by high-performance liquid chromatography. Characterization of the HAP microspheres
include particle size, size distribution, physical state of the drug in the microsphere, and microstructure of the drug delivery
system before and after in vitro release. The particle size, porosity, and morphology of the microspheres were dependent on
viscosity and concentration of the slurry as well as the atomization pressure used during spray drying. Even at the highest
drug load (2% wt/wt), the drug was present in a noncrystalline state. The drug release from the agglomerated microspheres
was quick and almost complete within 1 hour. However, compressing the same amount of agglomerated microspheres into an implant
greatly reduced the rate of ciprofloxacin release. Only 12% (wt/wt) of the drug was released from the implant within 1 hour.
The in vitro release of ciprofloxacin from these implants follows a diffusion-controlled mechanism. This method provides a
unique way of producing various shapes and drug loads of HAP microspheres that can be easily manufactured on a commercial
scale.
Published: January 28, 2002. 相似文献
12.
The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m
(99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural
polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment
efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron microscopy. Biodistribution
studies were performed by radiolabeling celecoxib (CS) and its microspheres (CMS) using99mTc and injecting arthritic rats intravenously. The geometric mean diameter of the microspheres was found to be 5.46 μm. In
vitro release studies indicated that the microspheres sustained the release of the drug for }6 days. Radioactivity measured
in different organs after intravenous administration of celecoxib solution showed a significant amount of radioactivity in
the liver and spleen. In case of celecoxib-loaded microspheres, a significant amount of radioactivity accumulated in the lungs.
No significant difference (P>.1) in the radioactivity was observed between the inflamed joint and the noninflamed joint following intravenous injection
of99mTc-CS. However, in case of the microspheres (CMS), the radioactivity present in the inflamed joint was 2.5-fold higher than
in the noninflamed joint. The blood kinetic studies revealed that celecoxib-loaded albumin microspheres exhibited prolonged
circulation than the celecoxib solution. 相似文献
13.
An antileishmanial compound, 14-deoxy-11-oxo-andrographolide, a derivative of andrographlide, isolated from the Indian medicinal plant Andrographis paniculata was evaluated for efficacy in free form and in different vesicular delivery modes on hamster model of Leishmaniasis. The subcutaneous injection of free drug reduced the spleen parasite load by 39%, whereas for drug incorporated in liposomes, niosomes and microspheres, reductions in the parasite load were 78%, 91% and 59%, respectively. Moreover, the drug in various delivery modes, particularly in liposomal and niosomal forms, showed no apparent immediate toxicity. Although an inverse linear relationship between the size of carriers and per cent efficacy in reduction of spleen parasite load was established, involvement of other factors such as drug release profiles or rates remains an open question. Because of greater efficacy and lesser toxicity, liposomal, niosomal and possibly microsphere-incorporated 14-deoxy-11-oxo-andrographolide might have clinical application to combat visceral Leishmaniasis. 相似文献
14.
Polylactide(PLA) microspheres were prepared using the solid-in-oil(S/O) spray-drying method to achieve the sustained release of a hydrophilic drug for the treatment of tuberculosis, via intratracheal instillation. Isoniazid(IN), a low-molecular-weight hydrophilic drug, was used as a model drug. The effects of various sizes of micronized IN powder, different drug/polymer ratios, spray-drying process parameters, and drug-release characteristics were studied to optimize the manufacturing parameters. A high entrapment efficiency(87.3%) was obtained using this method; furthermore, the microspheres were spherical and smooth. They were individually and homogenously distributed, with a mean diameter of 5.6 μm; furthermore, they showed a satisfactory extended sustained-release phase. After administration of the microspheres to rats, pulmonary drug concentrations were maintained at a relatively stable level for up to 4 weeks. 相似文献
15.
Madan Mohan Kamila Nita Mondal Lakshmi Kanta Ghosh Bijan Kumar Gupta 《AAPS PharmSciTech》2009,10(3):887-899
A multiunit floating drug delivery system of rosiglitazone maleate has been developed by encapsulating the drug into Eudragit® RS100 through nonaqueous emulsification/solvent evaporation method. The in vitro performances of microspheres were evaluated by yield (%), particle size analysis, drug entrapment efficiency, in vitro floating behavior, surface topography, drug–polymer compatibility, crystallinity of the drug in the microspheres, and drug release studies. In vitro release was optimized by a {3, 3} simplex lattice mixture design to achieve predetermined target release. The in vivo performance of the optimized formulation was evaluated in streptozotocin-induced diabetic rats. The results showed that floating microspheres could be successfully prepared with good yields (69–75%), high entrapment (78-97%), narrow size distribution, and desired target release with the help of statistical design of experiments from very small number of formulations. In vivo evaluation in albino rats suggested that floating microspheres of rosiglitazone could be a promising approach for better glycemic control. 相似文献
16.
Cell-penetrating peptides (CPPs) are widely used as drug carriers, owing to their superior ability to cross cell membrane both alone and with cargos, such as genes and other particles. Understanding the translocation mechanism of CPP is significant for many therapeutic purposes, including targeting drug and gene delivery. In this study, we performed a coarse-grained molecular dynamics simulation to investigate the interaction mechanism between polyarginine peptides and asymmetric membranes. Results showed that peptides can penetrate through the lipid bilayer by inducing a hydrophilic hole formation in the asymmetric membrane. Furthermore, the lengthy peptide chain length (R4–R16 peptides) and high membrane asymmetry positively affect peptide penetration. Our study provides insights into the molecular-level interactions between peptides and asymmetric membranes, as well as suggestions for targeted gene and drug delivery. 相似文献
17.
The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial
design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for
their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment
efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis
it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase
in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform
appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected
for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by
an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion
(D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr
2 values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion
kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained
with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful
for once-a-day intramuscular administration of ketorolac tromethamine.
Published: February 23, 2007 相似文献
18.
Purpose. This study was done to prepare, characterize, and evaluate salmon calcitonin (sCT) microspheres (ms) in vivo using a low molecular weight, hydrophilic 50∶50 poly (D,L-lactide-co-glycolide) polymer (PLGA).Methods. sCT ms were prepared by a dispersion/solvent extraction/evaporation process and characterized for drug content, particle size, surface morphology, and structural integrity of encapsulated peptide. Peptide stability and binding to the polymer was studied in 0.1 M phosphate buffer (PB), pH 7.4, and 0.1 M acetate buffer (AB), pH 4.0. Serum sCT levels were monitored for 2 weeks after subcutaneous injection of sCT ms to rats.Results. sCT ms were essentially free of discernible surface pores with a particle size distribution in the range of 16 to 89 mm and mean particle size of 51 and 53 mm for 2 batches. Fourier Transform Matrix-assisted Laser Desorption mass spectrometry of the extracted peptide showed that the encapsulation process did not alter its chemical structure. The peptide was substantially more stable in AB than in PB. Peptide binding to the polymer was dependent on pH and was markedly higher in PB than in AB. In vivo study proved that elevated serum sCT levels could be sustained for at least 10 days after administration of sCT ms to rats at a dose of 1.0 mg/kg.Conclusions. It was demonstrated that sCT could be incorporated into polymeric ms prepared from a low molecular weight, hydrophilic PLGA using a dispersion technique without altering molecular structure. A 2-week formulation was prepared at a dose of 1.0 mg/kg. 相似文献
19.
XiaoQing Dong Jun Xu WeiCai Wang Hao Luo XiaoFei Liang Lei Zhang HanJie Wang PengHua Wang Jin Chang 《中国科学C辑(英文版)》2008,51(11):1039-1044
In this study the w/o/w extraction-evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The microspheres were characterized
for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation
effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical
microspheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced
the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear
antigen (PCNA) in the epidermis layer with the microsphere treatment was significantly larger than those of the control groups.
Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy
for diabetic ulcer repair. 相似文献
20.
《Journal of liposome research》2013,23(3):307-319
AbstractChanging liposome physical, properties by designing vesicles with a hydrophilic/ steric barrier at the liposome surface has resulted in altered pharmacokinetics of these liposomes leading to increased blood levels of drug-carrying liposomes and reduced uptake by the RES. This discovery opens up new therapeutic opportunities for liposome-based drug delivery using hydrophilic coatings. Unravelling the mechanism of action of such coatings is an exciting challenge that will facilitate optimization of liposome surfaces for specific drug delivery applications. This article puts forward a series of assumptions and hypotheses to characterize the way hydrophilic coatings extend the plasma half-life of sterically - coated liposomes, to begin to explain how a steric barrier at the surface of liposomes may act. These speculations are examined in the light of current experimental evidence including that from non-liposome systems, and a model for particle removal from the circulation is proposed.IntroductionSince the days when liposomes were first conceived for drug delivery, ways have been sought to increase the length of time injected vesicles circulate in the body (1). In the mid-eighties, manipulation of the liposomal lipid composition increased the amount of time liposomes remained in the circulation for a well-defined but relatively limited design of 相似文献