Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15?000 microspheres possessed a smooth and round appearance with average particle size of 50?µm or so. The encapsulation percentages of microspheres prepared from PLGA 15?000, 20?000 and 30?000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30?000 microspheres to 3.97% of PLGA 15?000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30°C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15,000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Effects of process and formulation parameters on characteristics and internal morphology of poly(d,l-lactide-co-glycolide) microspheres formed by the solvent evaporation method.

Taking ABT627 as a hydrophobic model drug, poly-(lactic-co-glycolic acid) (PLGA) microspheres were prepared by an emulsion solvent evaporation method. Various process parameters, such as continuous phase/dispersed phase (CP/DP) ratio, polymer concentration, initial drug loading, polyvinyl alcohol concentration and pH, on the characteristics of microspheres and in vitro drug release pattern of ABT627 were investigated. Internal morphology of the microspheres was observed with scanning electron microscopy by stereological method. CP/DP is a critical factor in preparing microspheres and drug loading increased significantly with increasing CP/DP ratios accompanied by a remarkably decreased burst release. At CP/DP ratio 20, microspheres with a core-shell structure were formed and the internal porosity of the microspheres decreased with increasing CP/DP ratio. Increase in PLGA concentration led to increased particle sizes and decreased drug release rates. ABT627 release rate increased considerably with increasing PVA concentrations in the continuous phase from 0.1% to 0.5%. The maximum solubility of ABT627 in PLGA was approximately 30%, under which ABT627 was dispersed in PLGA matrix in a molecular state. Increase in initial drug loading had no significant influence on particle size, drug encapsulation efficiency, burst release and internal morphology. However, drug release rate decreased at higher drug loading. Independent of process parameters, ABT627 was slowly released from the PLGA microspheres over 30 days, by a combination of diffusion and polymer degradation. During the first 13 days, ABT627 was mainly released by the mechanism of diffusion demonstrated by the unchanged internal morphology. In contrast, a core-shell structure of the microspheres was observed after being incubated in the release medium for 17 days, independent of drug loading, implying that the ABT627/PLGA microspheres degraded by autocatalytic effect, starting from inside of the matrix. In conclusion, hydrophobic drug release from the PLGA microspheres is mainly dependent on the internal morphology and drug distribution state in the microspheres.     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

Lappaconitine-loaded microspheres for parenteral sustained release: effects of formulation variables and in vitro characterization

Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation.     

Effect of WOW process parameters on morphology and burst release of FITC-dextran loaded PLGA microspheres

Using fluorescein isothiocyanate labeled dextran (FITC-dextran 40, FD40) as a hydrophilic model compound, microspheres were prepared by a WOW double emulsion technique. Influence of process parameters on microsphere morphology and burst release of FD40 from PLGA microspheres was studied. Internal morphology of microspheres was investigated by stereological method via cryo-cutting technique and scanning electron microscopy (SEM). Drug distribution in microspheres was observed with confocal laser scanning microscopy (CLSM). Polymer nature (RG503 and RG503H) had significant influence on the micro-morphology of microspheres. Increase in continuous water phase volume (W2) led to increased surface porosity but decreased internal porosity. By increasing PVA concentration in the continuous phase from 0.1 to 1%, particle size changed marginally but burst release decreased from 12.2 to 5.9%. Internal porosity of microspheres decreased considerably with increasing polymer concentration. Increase in homogenization speed during the primary emulsion preparation led to decreased internal porosity. Burst release decreased with increasing drug loading but increased with drug molecular weight. Drug distribution in microspheres depended on preparation method. The porosity of microspheres decreased with time in the diffusion stage, but internal morphology had no influence on the release behavior in the bioerosion stage. In summary, surface porosity and internal morphology play a significant role in the release of hydrophilic macromolecules from biodegradable microspheres in the initial release phase characterized by pore diffusion.     

Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres I. Optimization of the drug incorporation into the polymer matrix and modelling of drug release

Bupivacaine has been encapsulated by solvent evaporation method based on O/W emulsion, using poly(DL-lactic-co-glycolic) acid (PLGA) 50:50. The particle size can be controlled by changing stirring rate and polymer concentration. The encapsulation efficiency was affected by polymer concentration and burst effect of bupivacaine released from particles was affected by drug/polymer mass ratio. Orthogonal design was used to optimize the formulation according to drug content, encapsulation efficiency and burst effect. The dissolution profile and release model were evaluated with two different bupivacaine microspheres (bupi-MS) groups including low drug loading (6.41%) and high drug loading (28.92%). It was observed that drug release was affected by drug loading especially the amount of drug crystal attached on surface of bupi-MS. The drug release profile of low drug loaded bupi-MS agreed with Higuchi equation and that of high drug loaded bupi-MS agreed with first order equation.     

微球的制备和表征

目的制备葡激酶突变体(K35R，DGR)的聚乳酸-羟基乙酸(PLGA)微球，使其在包封和释放过程中都能保持活性。方法使用复乳溶剂挥发法制备DGR的PLGA微球，研究了搅拌速度、PLGA浓度、内水相和外水相中的添加剂对蛋白包封率以及微球性质的影响，并进行了DGR微球的体外和体内释放试验。结果2%聚乙烯醇可以有效抑制超声乳化时DGR在水/二氯甲烷界面上的变性，将DGR的活性回收率从16%提高到几乎100%。在外水相中加入NaCl可以显著提高蛋白包封率，同时对微球的粒径分布和表面形态也产生了重要影响。DGR微球的体外释放呈现两个时相，15 d释放大约DGR总活性的50%。DGR微球在体内持续释放5 d。结论制备的PLGA微球，DGR包封率高，稳定性较好，是DGR的良好载药系统。     

Micromeritics and release behaviours of cellulose acetate butyrate microspheres containing theophylline prepared by emulsion solvent evaporation and emulsion non-solvent addition method

The present research work compares the effect of microsphere preparation technique on micromeritics and release behaviors of theophylline microspheres. Microspheres were prepared by oil-in oil (O₁/O₂) emulsion solvent evaporation method (ESE) using different ratios of anhydrous theophylline to cellulose acetate butyrate (CAB). Cyclohexane was used as non-solvent to modify the ESE technique (MESE method) and the effect of non-solvent volume on properties of microspheres was investigated. The obtained microspheres were analyzed in terms of drug content, particle size and encapsulation efficiency. The morphology of microsphere was studied using scanning electron microscope. The solid state of microspheres, theophylline and CAB were investigated using X-ray, FT-IR and DSC. The drug content of microspheres prepared by MESE method was significantly lower (15.54% ± 0.46) than microspheres prepared by ESE method (41.08 ± 0.40%). The results showed that as the amount of cyclohexane was increased from 2 mL to 6 mL the drug content of microspheres was increased from 15.54% to 28.71%. Higher encapsulation efficiencies were obtained for microspheres prepared by ESE method (95.87%) in comparison with MESE method (64.71%). Mean particle size of microsphere prepared by ESE method was not remarkably affected by drug to polymer ratio, whereas in MSES method when the volume of cyclohexane was increased the mean particle size of microsphere was significantly decreased. The ratio of drug to polymer significantly changed the rate of drug release from microspheres and the highest drug release was obtained for the microsphere with high drug to polymer ratio. The amount of cyclohexane did not significantly change the drug release. Although, x-ray showed a small change in crystallinity of theophylline in microspheres, DSC results proved that theophylline in microspheres is in amorphous state. No major chemical interaction between the drug and polymer was reported during the encapsulation process.     

Effects of salt addition on the microencapsulation of proteins using W/O/W double emulsion technique

The influence of co-encapsulation of stabilizing additives together with BSA on microsphere characteristics using the modified water-in-oil-in-water emulsion solvent evaporation (W/O/W) method was investigated. For this purpose, poly(L-lactide) microspheres containing bovine serum albumin (BSA) were prepared. The morphology, porosity, specific surface area, particle size, encapsulation efficiency and kinetics of drug release of protein loaded microspheres were analysed in relation to the influence of co-encapsulated stabilizing additives such as electrolytes. High salt concentrations in the internal (W1) aqueous phase, often necessary to stabilize protein or antigen solutions, led to an increase in particle size, particle size distribution, porosity and specific surface area. Bulk density and encapsulation efficiency decreased. The release profile was characterized by a high initial burst due to the highly porous structure. Addition of salt to the external or continuous water phase (W2), however, stabilized the encapsulation process and, therefore, resulted in improved microsphere characteristics as a dense morphology, a reduced initial burst release, a drastically increased bulk density and encapsulation efficiency. Analysis of the specific surface area (BET) showed that the addition of salt to W2, regardless of the salt concentration in the W1 phase, decreased the surface area of the microspheres approximately 23-fold. Microsphere properties were influenced by salts additions through the osmotic pressure gradients between the two aqueous phases and the water flux during microsphere formation. Release profiles and encapsulation efficiencies correlated well with the porosity and the surface area of microspheres. Furthermore, the influence of a low molecular weight drug and different time-points of salt addition to W2 on microsphere characteristics were studied by encapsulation of acid orange 63 (AO63), confirming the results obtained with BSA. This study suggests that modification of the external water phase by adding salts is a simple and efficient method to encapsulate stabilized protein solution, with high encapsulation efficiency and good microsphere characteristics.     

Effects of formulation parameters on encapsulation efficiency and release behavior of thienorphine loaded PLGA microspheres

To develop a long-acting injectable thienorphine biodegradable poly (d, l-lactide-co-glycolide) (PLGA) microsphere for the therapy of opioid addiction, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The thienorphine loaded PLGA microspheres were prepared by o/w solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, residual solvent content and sterility testing. The microspheres were sterilized by gamma irradiation (2.5 kGy). The results indicated that the morphology of the thienorphine PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 30.19?±?1.17 to 59.15?±?0.67μm and the drug encapsulation efficiency was influenced by drug/polymer ratio, homogeneous rotation speed, PVA concentration in the water phase and the polymer concentration in the oil phase. These changes were also reflected in drug release. The plasma drug concentration vs. time profiles were relatively smooth for about 25 days after injection of the thienorphine loaded PLGA microspheres to beagle dogs. In vitro and in vivo correlation was established.     

Preparation and in vivo evaluation of parenteral metoclopramide-loaded poly(alkylcyanoacrylate) nanospheres in rats

The influence of co-encapsulation of stabilizing additives together with BSA on microsphere characteristics using the modified water-in-oil-in-water emulsion solvent evaporation (W/O/W) method was investigated. For this purpose, poly(L-lactide) microspheres containing bovine serun albumin (BSA) were prepared. The morphology, porosity, specific surface area, particle size, encapsulation efficiency and kinetics of drug release of protein loaded microspheres were analysed in relation to the influence of co-encapsulated stabilizing additives such as electrolytes. High salt concentrations in the internal (W1) aqueous phase, often necessary to stabilize protein or antigen solutions, led to an increase in particle size, particle size distribution, porosity and specific surface area. Bulk density and encapsulation efficiency decreased. The release profile was characterized by a high initial burst due to the highly porous structure. Addition of salt to the external or continuous water phase (W2), however, stabilized the encapsulation process and, therefore, resulted in improved microsphere characteristics as a dense morphology, a reduced initial burst release, a drastically increased bulk density and encapsulation efficiency. Analysis of the specific surface area (BET) showed that the addition of salt to W2, regardless of the salt concentration in the W1 phase, decreased the surface area of the microspheres approximately 23-fold. Microsphere properties were influenced by salts additions through the osmotic pressure gradients between the two aqueous phases and the water flux during microsphere formation. Release profiles and encapsulation efficiencies correlated well with the porosity and the surface area of microspheres. Furthermore, the influence of a low molecular weight drug and different time-points of salt addition to W2 on microsphere characteristics were studied by encapsulation of acid orange 63 (AO63), confirming the results obtained with BSA. This study suggests that modification of the external water phase by adding salts is a simple and efficient method to encapsulate stabilized protein solution, with high encapsulation efficiency and good microsphere characteristics.     

Influence of preparation conditions on the properties of Eudragit microspheres produced by a double emulsion method

The aim of the present work was to study the preparation and characteristics of sustained‐release microspheres. As a model drug, sodium diclofenac was encapsulated in microspheres of the polymer Eudragit RS by using a double emulsion–solvent evaporation method. Investigations were carried out on the effects of the preparation method, the rate of the first step of emulsification, and the phase volume and composition (drug and additives) on the physical parameters of the product: its drug encapsulation, and the drug release. We evaluated the resulting microsphere structure [by differential scanning calorimetry (DSC)], the particle size, the surface area (by scanning electron microscopy), the entrapment and encapsulation efficiency (applying a novel method, energy‐dispersive x‐ray fluorescence analysis), the viscosity of the primary emulsion, and the organic solvent residue (by gas chromatography). We also evaluated and compared the samples by means of the kinetic data relating to drug release. The particle size could be decreased to one third by increasing the external aqueous phase ratio. In the first step of emulsification, elevation of the stirring rate led to microspheres with unfavorable characteristics. Increase of the active agent content and the plasticizer concentration had opposite effects. We applied a covalently not bound plasticizer, which was shown to influence the structure of the microspheres considerably. Drug Dev. Res. 64:41–54, 2005. © 2005 Wiley‐Liss, Inc.     

Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique

Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in?vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60?μm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5?μg VEGF (V5) and 50?μg VEGF (V50) per 500?mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27?ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.     

多孔利福平 PLGA 微球的制备工艺研究

目的：以利福平为模型药物,研究多孔聚乳酸—羟基乙酸共聚物（poly（lactic-co-glycolic acid）,PLGA）微球的最佳制备工艺。方法乳化溶剂扩散法制备多孔微球,采用扫描电镜观察微球形态,HPLC 法测定微球包封率。通过单因素考察实验,筛选影响微球形态和包封率的主要因素并优选条件。结果制备过程中 PLGA 种类、PLGA 浓度、致孔剂浓度、均质速度、外水相 PVA 浓度等影响微球的粒径、多孔结构和包封率。按优化工艺制备的微球平均粒径为8．6μm,密度为0．1 g·cm －3,易于吸入并提高肺部的沉积率。结论低密度多孔微球具有适宜的吸入特性和肺部沉积率,或可成为递送抗结核药物的新载体。     

Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 and PLGA 85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12-15 micron and 12-22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres

Etanidazole, a hypoxic radiosensitizer, has potential applications in radiotherapy. Due to its high solubility in water, common methods to encapsulate etanidazole into microspheres are not feasible. In this study, a spray-drying technique was employed to encapsulate etanidazole into the biodegradable polymer, PLGA65:35. Different fabrication conditions, such as polymer concentration, inlet temperature, feed rate, compressed air flow rate, aspirator ratio, as well as drug-loading were investigated to understand their effects on the particle size and distribution, encapsulation efficiency, and release behaviour. The effect on the morphologies of microspheres were also observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was demonstrated that most of these fabrication conditions influence either the droplet formation process or its subsequent evaporation and particle shrinking process, thereby determining the properties of the microspheres obtained. In many cases, temperature seems to be more important among all the factors considered. The present study demonstrates good fabrication conditions for producing the etanidazole-PLGA65:35-microspheres by using DCM as a solvent. The release of etanidazole from the spray dried PLGA65:35 microspheres was very fast, with an initial burst of 47% within the first 30 min and a cumulative release of over 80% within the first 5.5 h. The encapsulation efficiency of the drug in the microspheres varied with operating conditions from 69-96%.     

Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres

Etanidazole, a hypoxic radiosensitizer, has potential applications in radiotherapy. Due to its high solubility in water, common methods to encapsulate etanidazole into microspheres are not feasible. In this study, a spray-drying technique was employed to encapsulate etanidazole into the biodegradeable polymer, PLGA65:35. Different fabrication conditions, such as polymer concentration, inlet temperature, feed rate, compressed air flow rate, aspirator ratio, as well as drug-loading were investigated to understand their effects on the particle size and distribution, encapsulation efficiency, and release behaviour. The effect on the morphologies of microspheres were also observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was demonstrated that most of these fabrication conditions influence either the droplet formation process or its subsequent evaporation and particle shrinking process, thereby determining the properties of the microspheres obtained. In many cases, temperature seems to be more important among all the factors considered. The present study demonstrates good fabrication conditions for producing the etanidazole-PLGA65:35-microspheres by using DCM as a solvent. The release of etanidazole from the spray dried PLGA65:35 microspheres was very fast, with an initial burst of 47% within the first 30 min and a cumulative release of over 80% within the first 5.5 h. The encapsulation efficiency of the drug in the microspheres varied with operating conditions from 69-96%.     

PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。     

Sophoridine-loaded PLGA microspheres for lung targeting: preparation,in vitro,and in vivo evaluation

Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17?μm with 90% of the microspheres ranging from 12 to 24?μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4?h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10?μg/g for microspheres and 6.77?μg/g for solution after intraveneous injection for 30?min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.