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1.
目的制备肠溶包衣的胰岛素壳聚糖复合物纳米粒,并对其理化性质、体外释药以及在糖尿病模型大鼠体内的降血糖效果进行研究。方法采用离子交联法制备胰岛素壳聚糖复合物纳米粒,使用羟丙基甲基纤维素酞酸酯(HP55)对其进行肠溶包衣;通过扫描电子显微镜观察其表观形态,用激光粒度测定仪测定其粒径大小,用Zeta电势测定仪测定其Zeta电势,使用HPLC法测定离心上清夜中胰岛素浓度,计算包封率。结果制备得到的纳米粒均匀、圆整,包衣前后粒径分别为(281±10)nm和(328±13)nm,Zeta电势分别为(30.4±6.97)mV和(33.7±6.69)mV,包封率分别为78.5%和74.3%;肠溶包衣纳米粒在人工胃液和肠液中的释药速率均明显低于未包衣纳米粒,突释效应显著减小;未包衣复合物纳米粒能够显著降低糖尿病模型大鼠的血糖浓度,其降糖效果能持续20 h以上,肠溶包衣后,降糖效果明显增强;肠溶包衣前后在模型大鼠体内24 h相对生物利用度分别为11.12%和16.29%。结论肠溶包衣胰岛素壳聚糖复合物纳米粒可以有效抑制胰岛素的突释,促进其吸收,显著降低模型大鼠的血糖浓度,能够作为胰岛素口服给药的有效载体。  相似文献   

2.
《中国药房》2017,(1):46-49
目的:研究水飞蓟素肠溶聚乳酸-羟基乙酸共聚物(PLGA)纳米粒在大鼠在体肠灌流模型及结肠腺癌Caco-2细胞模型中的吸收特性。方法:采用高效液相色谱法测定水飞蓟素含量,考察水飞蓟素混悬液、水飞蓟素PLGA纳米粒和水飞蓟素肠溶PLGA纳米粒在大鼠在体肠灌流模型十二指肠、空肠、回肠和结肠的吸收速率常数(Ka)和表观吸收系数(Kapp)及其含低、中、高质量浓度(20、40、60μg/m L)水飞蓟素时在Caco-2细胞模型中的表观渗透系数(Papp)。结果:与水飞蓟素混悬液比较,水飞蓟素PLGA纳米粒和水飞蓟素肠溶PLGA纳米粒在十二指肠、空肠、回肠和结肠的Ka、Kapp均增加(P<0.05);与对应浓度水飞蓟素混悬液比较,含低、中、高质量浓度水飞蓟素的肠溶PLGA纳米粒和PLGA纳米粒在Caco-2细胞模型中的双向Papp均增加(P<0.05),其中水飞蓟素的肠溶PLGA纳米粒与PLGA纳米粒间差异无统计学意义(P>0.05)。结论:水飞蓟素肠溶PLGA纳米粒可有效增加水飞蓟素肠内吸收及Caco-2细胞摄取和跨膜转运速率。  相似文献   

3.
小檗碱壳聚糖纳米粒的制备及其体外释药特性研究   总被引:2,自引:0,他引:2  
目的:制备小檗碱壳聚糖纳米粒,并考察其外观、粒径和体外释药特性。方法:以离子凝胶法制备小檗碱壳聚糖纳米粒,紫外分光光度法测定小檗碱含量并计算其在不同递质中的累积释放度。结果:壳聚糖纳米粒呈球形或类球形,平均粒径267.9nm,多分散系数0.264,平均包封率(65.4±0.7)%。纳米粒6h内释放度为(56.8±1.7)%,8h以后趋于平缓,24h释放度为(65.6±1.1)%;在人工胃液、人工肠液和pH7.4磷酸盐缓冲液3种溶出递质6h内释放度依次为(75.3±1.3)%、(55.7±0.9)%、(45.8±1.6)%。结论:离子凝胶法适用于小檗碱壳聚糖纳米粒的制备,释药递质对释药程度影响显著,呈pH依赖性。  相似文献   

4.
壳聚糖包衣对胰岛素聚酯纳米粒胃肠道吸收的促进作用   总被引:11,自引:1,他引:11  
目的研究壳聚糖包衣胰岛素乳酸/羟基乙酸共聚物(PLGA)纳米粒对胰岛素胃肠道吸收的促进作用。方法以双乳化法制备了胰岛素PLGA复乳,壳聚糖用作稳定剂,制备了包衣纳米粒;观察了粒子大小、表面形态及Zeta电位;测定了包封率;考察了体外释药行为;以糖尿病大鼠评价降血糖水平。结果包衣纳米粒粒度分布均匀,隐约可见层状结构,壳聚糖可改变粒子表面Zeta电位,提高包封率,降低突释;灌服10 u·kg-1包衣纳米粒,14~16 h降血糖水平显著高于未包衣纳米粒(P<0.05),药理相对生物利用度提高到15.4%。结论壳聚糖包衣聚酯纳米粒可以促进胰岛素胃肠道吸收。  相似文献   

5.
目的:Box-Behnken设计-效应面法优化吴茱萸碱聚乳酸-羟基乙酸共聚物[poly (lactic-co-glycolic acid),PLGA]纳米粒处方(吴茱萸碱-PLGA纳米粒),考察体外释药行为。方法:单因素考察PLGA用量,油水体积比,泊洛沙姆188浓度,超声功率和时间等因素的影响,采用Box-Behnken响应面法优化吴茱萸碱-PLGA纳米粒处方。采用甘露醇为冻干保护剂,制备吴茱萸碱-PLGA纳米粒冻干粉末,并考察体外释药情况及释药模型。结果:吴茱萸碱-PLGA纳米粒最佳处方为:PLGA用量为445.1 mg、油水体积比1:5.2、泊洛沙姆188质量分数为1.2%。包封率和粒径分别为(75.73±1.33)%和(173.27±6.86) nm,与模型预测值接近。体外释药符合Higuchi模型:Mt/M=0.109 9t1/2+0.081 6,缓释特征明显。结论:Box-Behnken实验设计可用于吴茱萸碱-PLGA纳米粒处方研究,为进一步研究奠定了基础。  相似文献   

6.
目的制备供口服给药的胸腺五肽乳酸-羟基乙酸共聚物(thymopentin-poly lactic-co-glycolicacid;TP5-PLGA)纳米粒,并对纳米粒的物理性质进行考察。方法用复乳-溶剂挥发法制备TP5-PLGA纳米粒,以包封率为评价指标,用L16(45)正交设计优选纳米粒制备的处方工艺条件,用HPLC法测定胸腺五肽的含量,用激光粒度仪测定纳米粒的粒径,用透射电镜观察纳米粒的形态,用动态透析法考察纳米粒的体外释药特征。结果正交设计确定纳米粒制备的最优处方工艺条件为胸腺五肽质量浓度50 g.L-1,载体材料PLGA质量浓度100 g.L-1,乳化剂PVA质量浓度20 g.L-1;优化处方与工艺制备的纳米粒为规整的圆球形,平均粒径为(150.3±9.6)nm,载药量与包封率分别为(2.403±0.066)%与(28.12±0.60)%;体外释药结果表明,前5 h药物释放(31.27±1.5)%,存在一定突释,4 d累积释药量为(43.60±2.3)%。结论以乳酸-羟基乙酸共聚物为载体材料制备胸腺五肽纳米粒工艺简便,制剂具有良好的物理性质和体外释药特征。  相似文献   

7.
Liu XL  Zhang WJ  Wei G  Lu WY 《药学学报》2012,47(4):512-516
探索一种穿膜肽寡聚精氨酸[poly(arginine)8,R8]修饰的可生物降解乳酸/羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒作为胰岛素(insulin,INS)口服给药载体的可行性。采用复乳-溶剂挥发法制备包载胰岛素的PLGA纳米粒(INS-NP),R8经聚乙二醇桥联修饰于该纳米粒表面(R8-INS-NP)。对纳米粒进行理化性状表征及体外释放特性考察,并进行正常大鼠在体灌肠给药的药动学与药效学评价。所得纳米粒平均粒径为(179.0±5.2)nm,多分散系数为0.152±0.042,胰岛素包封率为(29.10±2.59)%,载药量为(5.05±0.50)%,体外释放呈先快后慢的两相模式。给药剂量为10 U.kg—1时,R8-INS-NP的降血糖效果显著优于同剂量的INS-NP,而且D-构型R8修饰的纳米粒(D-R8-INS-NP)吸收优于L-构型R8修饰的纳米粒(L-R8-INS-NP)。与皮下注射相比,INS-NP、L-R8-INS-NP和D-R8-INS-NP在体灌肠给药的相对生物利用度分别为0.52%、4.78%和8.39%,药理相对生物利用度分别为2.07%、3.90%和8.24%。纳米粒表面经R8修饰可促进其包载的胰岛素经肠道吸收,为实现多肽、蛋白类生物大分子口服给药提供了新思路。  相似文献   

8.
摘 要 目的: 制备辛伐他汀固体脂质纳米粒,并研究其经灌胃给药后在大鼠体内的药动学特征。方法: 采用热熔乳化超声 低温固化法制备辛伐他汀固体脂质纳米粒,考察辛伐他汀固体脂质纳米粒的粒径分布、Zeta电位、包封率、微观形态及体外药物释放特性。研究辛伐他汀固体脂质纳米粒经灌胃给药后在大鼠体内的药动学特征。结果: 辛伐他汀固体脂质纳米粒平均粒径为(242.5±62.1) nm,多聚分散系数为0.225±0.031,Zeta电位为(-32.1±4.2) mV,包封率为(95.7±2.6) %,在24 h内平稳缓慢释药。辛伐他汀固体脂质纳米粒在大鼠体内的Cmax和AUC0 t分别为辛伐他汀混悬液的2.89倍和1.83倍。结论:辛伐他汀固体脂质纳米粒在大鼠体内能快速吸收,显著提高了药物在大鼠体内的生物利用度。  相似文献   

9.
聚乳酸-羟基乙酸(PLGA)纳米粒表面特性是影响其体内分布的重要因素,经表面修饰的PLGA纳米粒已广泛应用于靶向给药系统研究.本文综述了PLGA纳米粒表面修饰的方法,包括共价交联、静电作用及疏水作用力等,概述了表面修饰纳米粒在非特异性生物黏附和生物渗透、特异性靶向、延长体循环时间及稳定生物活性分子方面的应用.  相似文献   

10.
目的:制备灯盏花素聚乳酸纳米粒并对其进行了表面修饰,同时考察了游离药物和纳米药物经大鼠尾静脉注射后在动物体内的药动学。方法:采用自乳化溶剂扩散法制备灯盏花素聚乳酸纳米粒,并用泊洛沙姆188对纳米粒进行表面修饰,采用反相高效液相色谱法(RP-HPLC)测定纳米粒的包封率、载药量和血浆样品中灯盏花素的含量,药时数据采用DASver 1.0药代计算程序处理。结果:载药纳米粒平均粒径为177.2和319.6 nm,多分散指数分别为(0.11±0.01)和(0.12±0.02),平均包封率及载药量分别为(86.9±0.9)%,(8.0±0.2)%和(93.1±0.6)%,(8.5±0.1)%,游离灯盏花素iv后呈二室模型,t1/2β为(0.81±0.14)m in,纳米组则呈一室模型,2种粒径的纳米粒的t1/2β分别为(8.90±0.16)m in(177.2 nm)和(13.90±0.07)m in(319.6 nm)。游离灯盏花素和2种粒径的灯盏花聚乳酸纳米粒的AUC0~t分别为(158.82±69.96),(1 476.25±51.22)和(704.95±25.39)mg.m in.L-1。经t检验,游离药物与纳米药物之间的t1/2β和AUC0~t均有统计学差异(P<0.01)。结论:灯盏花素制成纳米粒后明显增加了药物在动物体内的半衰期,延长了药物在体内的循环时间,且不同粒径的纳米粒对药动学有一定的影响。  相似文献   

11.
The anti‐leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24–74% with a short terminal half‐life of 1.5 h i.v. necessitating continuous infusion for 24–34 h for the treatment of leukemia. In the present study, etoposide‐loaded PLGA‐based surface‐modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA‐mPEG and PLGA‐PLURONIC copolymers were synthesised and used to prepared ETO‐loaded NPs by high‐pressure homogenization. The mean particle size of ETO‐loaded PLGA‐MPEG nanoparticles was 94.02±3.4 nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of −6.9±1.3 mV. ETO‐loaded PLGA‐pluronic nanoparticles had a mean particle size of 148.0±2.1 nm, an EE of 73.12±2.7%, and zeta potential value of −21.5±1.6 mV. In vitro release of the pure drug was complete within 4 h, but was sustained up to 7 days from PLGA‐mPEG nanoparticles and for 5 days from PLGA‐pluronic nanoparticles. Release was first order and followed non‐Fickian diffusion kinetics in both instances. ETO and ETO‐loaded PLGA nanoparticles labeled with 99mTc were used in blood clearance studies in rats where the two coated NPs, 99mTc‐ ETO‐PLGA‐PLU NP and 99mTc‐ ETO‐PLGA‐mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO‐loaded PLGA‐MPEG NP and PLGA‐PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228–239, 2010. © 2010 Wiley‐Liss, Inc.  相似文献   

12.
Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62?±?1.8% and 17.5?±?1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29?±?1.01% and 88.30?±?1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37°C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3?±?11% and 62.7?±?3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.  相似文献   

13.
The present investigation was aimed at developing PEGylated PLGA nanoparticles of cytarabine. PLGA Nanoparticles were prepared by modified nanoprecipitation method, optimized for mean particle size (152?±?6?nm) and entrapment efficiency (41.1?±?0.8%) by a 32 factorial design. The PEGylated PLGA nanoparticles of cytarabine had a zeta potential of ?7.5?±?1.3?mV and sustained the release of cytarabine for 48?h by Fickian diffusion. The IC50 values for L1210 cells were 6.5, 5.3, and 2.2?µM for cytarabine, cytarabine loaded PLGA nanoparticles and cytarabine loaded PLGA-mPEG nanoparticles respectively. Confocal microscopy and flow cytometry showed that the nanoparticles were internalized by the L1210 cells and not simply bound to their surface. Biodistribution studies showed that the PEGylated nanoparticles of cytarabine were present in significantly higher concentrations in blood circulation as well as in brain and bones and avoided RES uptake as compared to the free drug.  相似文献   

14.
Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62 +/- 1.8% and 17.5 +/- 1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29 +/- 1.01% and 88.30 +/- 1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37 degrees C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3 +/- 11% and 62.7 +/- 3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.  相似文献   

15.
The aim of the present work was to investigate the preparation of PLGA nanoparticles (PNP) and PLGA-Hp55 nanoparticles (PHNP) as potential drug carriers for oral insulin delivery. The nanoparticles were prepared by a modified emulsion solvent diffusion method in water, and their physicochemical characteristics, drug release in vitro and hypoglycemic effects in diabetic rats were evaluated. The particle sizes of the PNP and PHNP were 150+/-17 and 169+/-16 nm, respectively, and the drug recoveries of the nanoparticles were 50.30+/-3.1 and 65.41+/-2.3%, respectively. The initial release of insulin from the nanoparticles in simulated gastric fluid over 1 h was 50.46+/-6.31 and 19.77+/-3.15%, respectively. The relative bioavailability of PNP and PHNP compared with subcutaneous (s.c.) injection (1 IU/kg) in diabetic rats was 3.68+/-0.29 and 6.27+/-0.42%, respectively. The results show that the use of insulin-loaded PHNP is an effective method of reducing serum glucose levels.  相似文献   

16.
Insulin is the most effective and durable drug in the treatment of advanced stage diabetes. However, oral delivering insulin was a tough task for rapid enzymatic degradation. In this work, we designed and developed a delivery system composed of enteric nanosphere for oral delivery of insulin. The silica was selected for loading insulin, which surface has a lot of pores with a powerful adsorption capacity, advantages for permeability and slow-release. The insulin-loaded silica (Ins-SiO2) was prepared by adsorption in HCl solution. The Ins-SiO2 obtained was coated with the hydroxypropyl methylcellulose phthalate (HP55) by desolvation method, which is a good enteric coating material. The Ins-SiO2-HP55, an enteric nanosphere of insulin obtained were characterized by transmission electron microscope (TEM), surface area, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results showed that insulin was loaded most in the pores of silica, while the HP55 coated on the extent of Ins-SiO2. In vitro drug release results revealed that the release of insulin from Ins-SiO2-HP55 was markedly reduced in simulated gastric fluid (SGF). By contrast, the release amount of insulin from Ins-SiO2-HP55 was increased significantly in simulated intestinal fluid (SIF). In vivo evaluation on diabetic animals showed the blood glucose level of diabetic rats could be effectively reduced after oral administration Ins-SiO2-HP55. There is marked hypoglycemic effect after 1 h of taking the Ins-SiO2-HP55. After 3 h, the GLU of rats of the Ins-SiO2-HP55 stably kept from 4.85 to 2.67 mmol/L that was significantly less than the normal level (6.7 mmol/L). However, that of rats taking raw insulin kept from 8.03 to 6.56 mmol/L that is higher than the normal level. These results suggested that Ins-SiO2-HP55 could have potential value in oral administration systems of diabetes chemotherapy.  相似文献   

17.
Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7?±?2.0%, 41.8?±?1.9%, and 45.3?±?2.2%; drug loadings 3.87?±?0.20%, 2.79?±?0.13% and 3.02?±?0.15%; yield 85.2?±?3.0%, 86.9?±?4.6% and 76.9?±?2.1%; particle sizes 116.6?±?4.5, 143.0?±?3.8 and 134.1?±?5.2?nm; and zeta potential ?15.0?±?4.96, ?13.8?±?5.26 and ?13.9?±?5.14?mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.  相似文献   

18.
PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks?=?645?M?1). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4?±?2.53?nm and???31.9?±?(?3.08)?mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3?±?0.11?µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency.  相似文献   

19.
Chitosan nanoparticles loaded with insulin (IN-CS-NPs) were prepared using ionic gelation method using sodium tripolyphophate as a crosslinker. Later the nanoparticles (NPs) were dispersed in buccal films. The physicochemical properties and the morphology of the nanoparticles were characterized. The stability and release of insulin from the NPs were investigated. Buccal films were prepared separately and their properties such as the weight, thickness, pH, and mucoadhesiveness were investigated. The best film was used to disperse IN-CS-NPs and the loaded film was characterized. The nanoparticles size, polydispersity index, zeta potential, entrapment efficacy, and the loading capacity were 325.07?±?1.32?nm, 0.38?±?0.03 and 8.41?±?0.80?mV, and 73.27 and 18.03%, respectively. The weight and thickness of the loaded film with IN-CS-NPs were 23.0?±?3.0?mg and 0.32?±?0.04?mm, respectively and the mucoadhesive force was 2.3?±?0.2 N. The drug was stable in the NPs and in the films for three months, and its release was controlled by the film and the nanoparticles. Finally, the films loaded with IN-CS-NPs were studied in vivo and were compared to the commercially available insulin. The films prepared in this work were found to decrease glucose level significantly in diabetic rats.  相似文献   

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