32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

32P-磷酸铬-聚 L-乳酸缓释粒子的制备及其放射性释出和生物分布

Objective The aim of this study was to prepare the 32P-chromic phosphate-poly(L-lac-tide) (32P-CP-PLLA) particles with different ratio of the materials and further examine their performance in-dex in vivo and in vitro and their intracorporeal distribution. Methods The erosion, degrading rates, de-layed release velocity and radioactivity self-absorption coefficient (RSAC) of 32P-CP-PLLA particles made from different materials were investigated and compared. After the implantation of 32P-CP-PLLA particles and the injection of 32P-CP colloids in the muscular tissues, the weight loss rate and the radioactivity release rate (RRR) of the particles were calculated. The intracorporeal distribution, radioactive half-life and bio-logical effect of 32P in the targeting sites were further studied. Statistical analysis was performed with SPSS 12.0, and one-way analysis of variance and t-test were used. Results 32P-CP-PLLA particles were of green cylinder, with regular shape and radionuclide distribution. The RSAC of the particles was of little re-lation with molecular weight of PLLA and proportional to the ratio of PLLA to CP. The extracorporeal release rate increased with the reduction of molecular weight of PLLA and with the increase of the ratio of PLLA to CP. The RRR reached peak when PLLA was 3 times of CP. The 32P-CP, released with the degradation and corrosion of the particle distributed mainly in the surrounding muscles of the particle. And the peak of per-centage activity of injection dose per gram of tissue (% ID/g) in liver, spleen and bone were 1. 7887, 1. 6401 and 1. 9470 respectively, much lower than that in the 32P-CP group (4.7523, 3.9712 and 4.3174 ; all t > 2.7, all P < 0.05). The % ID/g in other organs was much less. The radioactivity effective half-life in the targeting sites increased to about 13 d. There was widespread necrosis around the particles with no ex-istence of normal tissues among them. And no abnormality in spleen and liver was found. Conclusion As a better dosage form of pure β-particle emitter, 32P-CP-PLLA, which can increase the targeting radioactive dosage and effective half-life in the implanting sites, can be served as an potential implanting agent for onco-therapy with a better perspective.     

常用的蛋白质保护剂对NGF-PLGA微球性质的影响

目的研究常用的蛋白质保护剂对微球性质的影响特点。方法复乳化溶剂挥发法制备NGF-PLGA微球,分别添加葡萄糖,聚乙二醇,卵清蛋白作保护剂,观察微球的形态,载药量、包封率及体外释放特点,研究保护剂的作用特点。结果保护剂对微球的粒径、包封率和载药量影响不明显,粒径集中分布在10-40μm,载药量0．0007％-0．0011％,包封率7％～11％。保护剂主要影响微球的形态和体外释放。添加不同的保护剂,微球表面的光滑度和孔隙差别较大;体外释放的突释较小,存在明显的缓慢释放期,进入快速释放期的起始时间和释药速度受保护剂影响显著,一个月内的累积释放药量达到80％以上。结论保护剂的分子量可能是微球形态和释放不同的原因,添加分子量大的保护剂形成的微球的表面比添加分子量小的保护剂时致密光滑,体外的缓慢释放期长。     

多孔聚乳酸-聚乙醇酸共聚物作为缓释重组人骨形态发生蛋白-2载体的实验研究

目的 探讨多孔聚乳酸-聚乙醇酸共聚物(PLGA)作为重组人骨形态发生蛋白-2(rhBMP-2)的载体，通过体外释放试验和体内活性试验来评价rhBMP-2释放的动力学过程及活性。方法 采用乳液冷冻干燥法制作含rhBMP-2缓释系统的PLGA支架，支架进行扫描电镜观察；采用高效液相色谱分析仪检测不同时间点释放液中rhBMP-2的含量，进行累积释放量的动态观察；将缓释rhBMP-2支架植入SD大鼠大腿股部肌袋内，分别在不同时间点进行组织学观察。结果 支架材料的形态学观察显示，材料表面呈多孔状；rhBMP-2从支架中释放的动力学过程为第1天表现为爆发性释放(30.0％)，以后缓慢持续释放，至1个月左右释放量达80.6％；活性评价结果显示，rhBMP-2缓释支架组可见新生骨组织形成伴较多的骨母细胞排列，无rhBMP-2支架组则无成骨现象。结论 多孔PLGA可作为rhBMP-2的缓释载体，并具有良好的生物活性，可作为骨组织工程研究中的新型支架，同时具有临床应用的可行性。     

In vitro release of vascular endothelial growth factor from gadolinium-doped biodegradable microspheres.

A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 +/- 18 microm. The gadolinium loading was 17 +/- 3 microg/mg polymer and the VEGF loading was 163 +/- 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of approximately 6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI.     

重组人表皮细胞生长因子缓释微球治疗糖尿病大鼠溃疡

目的 制备重组人表皮细胞生长因子(rhEGF)缓释微球,并对其形貌、释药行为和在体外促进细胞增殖的能力进行评价;同时比较rhEGF缓释微球与rhEGF原液对糖尿病大鼠溃疡促愈作用的差异. 方法 (1)用改进的复乳法制备rhEGF缓释微球.透射电镜检测rhEGF微粒形貌表征,激光粒度仪/Zeta电位仪分析微球粒径分布,ELISA法测定rhEGF微球释药行为.(2)以小鼠成纤维细胞L929细胞系为对象,采用MTT法鉴定rhEGF缓释微球的生物学活性.(3)制备糖尿病大鼠溃疡模型,成模后采用随机数字表法将大鼠分为4组:rhEGF缓释微球组(A组)、rhEGF原液组(B组)、空白微球组(C组)、PBS溶媒对照组(D组),每天给药1次.分别于给药后3,7,14,21 d对溃疡创面照相计算创面愈合率.创缘皮肤取材,测定羟脯氨酸含量,免疫组化检测β1整合素和角蛋白-19并测量其阳性染色面积比. 结果 (1)rhEGF缓释微球平均粒径为193.5nm,粒径分布均匀,微球之间元粘连,分散性好.释药过程符合Higuchi释放动力学模型,释放时间长达24 h.(2)不同浓度rhEGF缓释微球均有促进小鼠成纤维细胞增殖的作用,其中以10μg/L浓度促小鼠成纤维细胞增殖的作用最强.(3)从治疗第7天开始,愈合率以A组最快,A组与其他三组比较,差异均有统计学意义(P<0.05).羟脯氨酸含量、β1整合素和角蛋白-19阳性染色面积比A组均高于B组. 结论 用改进的复乳法制备的rhEGF缓释微球,粒径大小分布均一,释放时间长达24 h.rhEGF缓释微球促进糖尿病大鼠溃疡创面愈合速度较rhEGF原液更快,溃疡创面愈合质量更高.     

PLGA微米与纳米载药颗粒用于药物携带与递送的比较研究

 

目的 通过评价聚乳酸-羟基乙酸共聚物(polylactic acid-glycolic acid copolymer,PLGA)微米颗粒(micron particle,MP)与纳米颗粒(nanoparticle,NP)的表面特征、载药能力、药物缓释能力及细胞吞噬能力等方面来比较阐述PLGA纳米与微米颗粒在细胞预处理与修饰中的合理应用。方法 分别制备PLGA纳米颗粒与微米颗粒,并进行表征;随后,比较其载药能力,并对药物的释放特征进行测定;最后,在不同时间点通过荧光强度评价两种颗粒与细胞结合或进入细胞的能力。结果 所制备的纳米粒与微米颗粒粒径分别分布在200~300 nm和2~4 μm;两种颗粒载药量相当,分别为14.3%和14.1%;在药物缓释方面,纳米颗粒存在显著的早期突释现象;微米颗粒释放缓慢,持续缓释可达一周左右;粒径相对小的纳米粒更容易进入或与细胞结合,共孵育12 h即达到最大值,微米颗粒相对较慢,最大值出现在共孵育24 h后。结论 PLGA纳米颗粒作为药物载体更适合于急性组织或细胞保护,微米颗粒更适合于慢性持续性保护。

     

尼索地平微球体外释药的研究

 目的研究尼索地平缓释微球的体外释药行为.方法建立检测尼索地平微球释药量的高效液相色谱法(HPLC),考察自制微球在3种释放条件下的释药情况.结果动态透析法能较好地反映微球的实际释药行为.微球的体外释药行为的拟合方程为:1-Q=0.7610(1-t/too)3+0.1901(r=0.9983).结论微球释药缓慢而平稳.     

脑源性神经营养因子PLGA纳米粒的处方工艺研究

目的制备脑源性神经营养因子聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,使用星点设计-效应面法对处方工艺进行优化筛选。方法以生物降解型聚乳酸-羟基乙酸共聚物为载体材料,采用复乳化溶剂挥干法制备脑源性神经营养因子PL-GA纳米粒。观察纳米粒的形态、大小和粒径分布。以PLGA的用量及形成复乳时PVA含量为考察因素,体外释放为评价指标,用线性方程和二次及三次多项式描述体外释放和两个影响因素之间的数学关系,根据最佳数学模型描绘效应面,选择最佳处方,并进行预测分析。结果各指标的三项式拟合方程均优于多元线形回归方程,建立的数学模型的预测值与实际值符合较好。结论用星点设计-效应面法优化处方工艺预测性良好。     

Morphology and release kinetics of technetium-99m(V) dimercaptosuccinic acid loaded, poly(lactic-co-glycolic)acid microspheric delivery system. An experimental approach that may be used for targeted radiation treatment

The aim of our studies was to formulate a system that delivers the required radiation dose to the tumor site and minimize the harm to other organs or tissues. The poly (lactic-co-glycolic acid, 75:25; 50:50) microspheric radiation delivery system was fabricated using double emulsion solvent evaporation technique for the encapsulation of technetium-99m(V)dimercaptosuccinic acid ((99m)Tc(V)DMSA). Microspheres of different sizes (0.2-20.0 mum) were prepared. The initial burst in microspheres with 10% and 1% poly vinyl alcohol (PVA) in the presence of poly ethylene glucol (PEG) was as 30% and 16% respectively, however the initial burst in microspheres without the PEG was 9% and 1.2% respectively. The results indicated that smaller microspheres had higher encapsulation (68%) of (99m)Tc(V)DMSA than larger microspheres (15%). The stirring rate changed the surface of the microspheres from smooth spherical, to spherical, porous. The ratio of co-polymers (75:25/50:50) affected the release kinetics. In conclusion, our studies with varied surfactant concentrations, co-polymer concentrations and speed of solvent evaporation, on the morphology and release kinetics of (99m)Tc(V)DMSA from the microspheres, may be applied for the fabrication of targeted radiotherapeutic microspheres by substituting (99m)Tc(V)DMSA with rhenium-188 (V) DMSA ((188)Re(V)DMSA). (188)Re(V)DMSA is a therapeutic analogue of (99m)Tc(V)DMSA and both share similar radiopharmaceutical properties.     

Photodynamic antimicrobial chemotherapy through photosensitizers loaded poly-l-glycolic acid on Candida albicans in denture lining material: Release,biological and hardness study

AimThe aim of this in-vitro study was to formulate poly-l-glycolic acid nanoparticles loaded with methylene blue (PLGA-MB) and to characterize their physicochemical features, photosensitizer-release kinetics and antimicrobial efficacy against Candida albicans (C. albicans) after incorporating in polymethyl methacrylate (PMMA) denture lining materials.Material and methodsMB-PLGA nanoparticles were synthesized according to the modified nanoprecipitation method. The morphological characterization of the nanoparticles was studied under scanning and transmission electron microscope. Particle size, surface charge, polydispersity index (PDI) and MB release were evaluated. The effect of 660 nm semiconductor AlGaInP diode laser on C. albicans was studied in vitro. The PMMA was weighed and PLGA free and PLGA-MB were added in the lining material according to the weight percentage as 2.0 wt.% and 5.0 wt.% and tested for the diameter of the inhibition zones of C. albicans growth and shore A hardness.ResultsHomogenous spherical nanoparticles with round morphology with size ranging between 60–80 nm were observed while PLGA-MB were seen to have irregular structure within the nanoparticle under TEM. PLGA-Free was larger in size than the loaded PLGA (∼62 nm) that evidenced reduction in size by adding the MB photosensitizer. PDI recordings reduced from 0.198 for the PLGA-Free nanoparticles to 0.164 for the PLGA-MB nanoparticles. The entrapment efficiency of MB inside PLGA showed an average percentage of ∼75 % uptake that resulted in the overall loading of ∼15 %. An overall inhibition of 78 %, 41 % and 28 % of C. albicans growth was seen with a concentration of 0.1, 0.5 and 1.0 μg/mL, respectively. The application of PLGA nanoparticles loaded with MB evidenced >75 % of C. albicans. MB incorporation did not lead to a clinically relevant change on shore A hardness.ConclusionPLGA loaded with MB is believed to have promising target therapy against C. albicans in denture soft lining materials in terms of PACT in vitro. The synergistic association between PLGA and MB proved enhanced antifungal activity. PLGA-MB could be an important tool in nanobiotechnology and photodynamic therapy for novel formulations with higher antimicrobial efficacy and improved drug delivery from denture soft lining materials.     

多西他赛热敏脂质体的制备及含量和包封率的测定

目的制备多西他赛(DTX)热敏脂质体(docetaxel-loaded thermosensitive liposomes,DTL),建立其含量和包封率测定方法。方法采用薄膜分散法制备DTL并用高效液相色谱法(HPLC)测定脂质体中多西他赛的含量。采用高速离心法分离脂质体与游离药物并测定包封率。结果制备的DTL粒径均一,平均粒径为104 nm,相变温度为42.20℃。辅料和溶剂不干扰主药含量测定,线性范围为1.0～100.0μg/ml(r=1);多西他赛平均回收率为99.50%(RSD=0.65%)。药物在脂质体中的包封率大于98%。结论薄膜分散法可用于制备DTL。药物含量和包封率测定方法简便快速,准确可靠,专属性强。