The clinical efficiency and complication analysis of dexamethasone sustained release intraocular implantation in macular edema after vitrectomy / 中国医师杂志

Objective:To investigate the efficiency, safety and complication of 0.7 mg dexamethasone sustained release agent (Ozurdex ?) vitreous cavity implantation for macular edema secondary to vitrectomy. Methods:A total of 15 patients (16 eyes) were included in this retrospective case series study. There were 7 males (8 eyes) and 8 females (8 eyes). Age ranged from 47 to 72 years old with an average age of (60.2±8.6)years. Among them, 8 cases were diabetic retinopathy (6 cases combined cataract surgery). 4 cases were silicone oil removal after retinal detachment surgery (all combined cataract surgery). 2 cases were epi-macular membrane (all combined with cataract surgery) and 1 case was vitreous hemorrhage (combined with cataract surgery). Ozurdex ? was implanted for macular edema after vitrectomy. The number of implantation was from 1 to 3 times (mean 1.67 times). The follow-up time was from 3 to 12 months, with an average of (7.33±3.50)months. Results:The best corrected visual acuity (BCVA) was improved in 10 cases (11 eyes), unchanged in 4 cases and decreased in 1 case within 3 months after Ozurdex ? implantation in the 15 cases (16 eyes). The macular edema was significantly improved in all cases. The central macular thickness (CMT) measured by optical coherence tomography (OCT) was from 350 to 1 370 γm before surgery with average thickness (621.60±235.48)γm, and the CMT postoperative was 118 to 556 γm with average thickness (269.87±118.14)γm, with statistically significant difference ( P<0.001). Cataract was not progressive after Ozurdex ? implantation. Macular edema was recurrent in 7 cases after first implantation and stable for additional 1-2 injections. Intraocular pressure elevation occurred in 3 cases 1 to 2 months after implantation with the highest intraocular pressure of 36 mmHg, which were controlled by local anti-glaucoma eye drops. Drugs entered into the anterior chamber in 2 cases and was taken out in 1 case. Conclusions:The efficiency of Ozurdex ? vitreous cavity implantation is definite and the complications are controllable, so it is a safe and effective method to treat macular edema after vitrectomy.

Desarrollo de implantes subcutáneos de liberación controlada de Carvedilol para la reducción sostenida de la presión arterial en modelos experimentales de hipertensión arterial / Development of Subcutaneous Implants of Controlled Release Formulations of Carvedilol for Sustained Blood Pressure Reduction in Experimental Models of Hypertension

RESUMEN Objetivo: El objetivo del presente estudio fue el desarrollo y la evaluación farmacocinética y farmacodinámica de la liberación in vivo de implantes subcutáneos de carvedilol capaces de aportar niveles tisulares estables en modelos experimentales de hipertensión arterial. La incorporación del polímero hidrofílico SoluPlus (SP) en los implantes PCL:SP 150:150 y 50:250 favorece un incremento de la liberación de carvedilol dado que aporta concentraciones plasmáticas en el rango de 100-200 ng/mL durante 2 semanas, lo que tiene como resultado una reducción sostenida de la presión arterial sistólica indirecta en animales SHR. Material y métodos: Se prepararon implantes subcutáneos de poli (epsilon-caprolactona) (PCL) con diferentes proporciones del polímero hidrofílico SoluPlus (300:0; 250:50; 150:150 y 50:250 mg) cargados con 100 mg de carvedilol. Se evaluó el perfil plasmático y el efecto sobre la presión arterial sistólica (PAS) luego del implante de cada formulación en el tejido subcutáneo de ratas espontáneamente hipertensas (REH) macho. Resultados: Las formulaciones PCL:SP 50:250 y 150:150 aportaron niveles en el rango de 100-200 ng/mL. Las formulaciones PCL:SP 250:50 y 300:0 aportaron concentraciones inferiores de carvedilol comprendidas en el rango de los 0-100 ng/mL durante el transcurso del tratamiento. Los animales espontáneamente hipertensos tratados con PCL:SP 50:250 y 150:150 experimentaron un descenso significativo de la presión arterial sistólica (PCL:SP 50:250: DPAS: -36,6 ± 2,0 mmHg; PCL:SP150:150: 35,7 ± 2,2 mmHg; p <0,05 vs. basal). Conclusiones: La incorporación del polímero hidrofílico SoluPlus en los implantes PCL:SP 150:150 y 50:250 favorece un incremento de la liberación de carvedilol, ya que aporta concentraciones plasmáticas del β-bloqueante que aseguran una reducción sostenida de la PAS indirecta en animales espontáneamente hipertensos.

ABSTRACT Objective: The aim of this study was the development and pharmacokinetic/pharmacodynamic evaluation of the in vivo release of subcutaneous implants of carvedilol capable of providing stable tissue levels in experimental models of hypertension. Methods: The subcutaneous implants were prepared with poly (epsilon-caprolactone) (PCL) and different proportions of the SoluPlus (SP) hydrophilic polymer (300:0; 250:50; 150:150 and 50:250 mg) loaded with 100 mg carvedilol. The plasma profile and the effect on systolic blood pressure (SBP) after subcutaneous implantation of each formulation was evaluated in male spontaneously hypertensive rats (SHR). Results: The PCL:SP 50:250 and 150:150 formulations provided levels ranging from 100 to 200 ng/mL and the PCL:SP 250:50 and 300:0 formulations provided lower concentrations of carvedilol ranging from 0 to 100 ng/mL during the treatment period. Spontaneously hypertensive animals treated with the PCL:SP 50:250 y 150:150 implants presented a significant decrease in SBP (PCL:SP 50:250: DPAS: -36.6 ± 2.0 mm Hg; PCL:SP150:150: -35.7 ± 2.2 mmHg; p <0.05 vs. baseline values) Conclusions: The incorporation of the SoluPlus hydrophilic polymer in PC:SP 150:150 and 50:250 implants increases the release of carvedilol, since it provides plasma concentrations ranging from 100 to 200 ng/ml, resulting in a sustained reduction of indirect SBP in SHR.

Pharmacokinetics and bioequivalence of gliclazide modified release tablets in Beagle dogs / 第二军医大学学报

Objective: To explore the pharmacokinetics of self-made gliclazide modified release tablets in Beagle dogs and to evaluate the in vivo and in vitro correlation. Methods: Six Beagle dogs were orally given self-made gliclazide modified release tablets or reference preparation (DaMeiKang) at a dose of 30 mg with self-control cross-over method. Blood samples were collected at different time points after administration. The gliclazide concentration in plasma was determined by high-performance liquid chromatography, and the pharmacokinetic parameters were calculated. The pharmacokinetic characteristics and relative bioavailability of self-made gliclazide modified release tablets were investigated, the bioequivalence was evaluated, and the in vivo and in vitro correlation was calculated. Results: Area under curve (AUC0-∞) of DaMeiKang was (101.74 ± 20.29) μg/(mL · h), and AUC0-∞ of self-made gliclazide modified release tablets was (95.40 ± 28.68) μg/(mL · h). There were no significant differences in the pharmacokinetic parameters between the test and reference formulations (P>0.05). The relative bioavailability of self-made gliclazide modified release tablets was 93.77%, which was bioequivalent with the reference preparation. The in vitro and in vivo correlation analysis showed that the correlation coefficients of DaMeiKang and self-made gliclazide modified release tablets were 0.912 and 0.894, respectively, which were higher than the critical value (r005.7=0.754). The in vitro release rates of the two preparations were correlated with the in vivo absorption rates. Conclusion: The self-made gliclazide modified release tablets have sustained-release characteristics and bioequivalence with reference preparation. The in vivo absorption behavior of gliclazide modified release tablets can be predicted by the in vitro release assay established in this study.

Fabrication and biological effect investigation of the antibacterial drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface / 中华骨科杂志

Objective To fabricate an antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface,and to investigate its surface characteristics,swelling behavior,drug release behavior in vitro,antiinfection performance in vivo,and tissue biocompatibility.Methods Cross-linked starch (CSt) was synthesized first and then CSt was loaded with gentamicin (GEN) as a carrier (GEN@CSt),then 4-arm-polyethylene glycol (PEG) was added to it which was mixed by ultrasound.The surface of titanium (Ti) was covered with a layer of poly dopamine (PDA).The drug-loaded hydrogel was fixed to the titanium surface,subsequently capped by poly lactic-co-glycolic acid (PLGA) membranes,and then the Ti-PDA-PEG (GEN@CSt)-PLGA composite coating was fabricated finally.Surface morphology of the system was observed,while the swelling behavior was characterized;release behavior of the composite coating was detected;the bacteriostatic experiments were carried out with staphylococcus aureus (SAU),staphylococcus epidermidis (SEP) and escherichia coli (ECO) in vitro.The animal models of infected bone defect was established in 36 New Zealand white rabbits.These animals were randomly divided into three groups.Group 1 animals were implanted with drug-loaded composite coatings.Group 2 animals were implanted with drug-free composite coatings.Group 3 animals were implanted with bare titanium rods.The infection data were collected periodically to carry out antiinfection experiments in vivo.Another 12 rabbits were divided into the experimental group and the control group randomly.Biocompatibility of the materials was observed by histopathology after implantation of the corresponding materials into the femoral condyle.Results The composite coating adhered to the titanium surface firmly,presenting a smooth and translucent shape.The ratio of CSt/PEG affects swelling behavior varied,starch-free gels maintained an equilibrium swelling of 7.4,after the ratio reached 1 ∶ 1,the equilibrium swelling ratio remained at 3.0.In-vitro the release rate of the first 8 h was fast,and the cumulative release amount accounted for 83％ of the total in the first 7 days,lasting more than 13 d.In vitro antibacterial test,the average diameter of the inhibition ring was 3.6±0.13 cm (SAU),3.4±0.11 cm (SEP),3.7±0.10 cm (ECO).In-vivo anti-infection experiment,the infection situation of the group 1 was better than the control groups 2 and 3.The pathological results indicated that inflammatory reaction in the experimental group was basically the same as the control group.Conclusion The study successfully fabricated the antibacterial controlled drug delivery system with PEG-hydrogel and gentamicin-loaded-CSt on titanium surface.The system has a reasonable drug release behavior,and effectively inhibited the growth of bacteria in vivo and in vitro.It also has good biocompatibility to stand a promising strategy to improve the orthopedics anti-infection.

Trans-scleral ocular drug delivery for the treatment of posterior segment eye diseases / 中华眼底病杂志

The human sclera accounts for 95％ of the surface of the eyeball,providing ample contact area which is suitable for targeted trans-scleral ocular drug delivery.Currently there are several tans-scleral sustained-release strategies,including intra-scleral delivery,episcleral delivery,as well as tans-scleral iontophoresis.Different devices and methods have their own advantages and disadvantages,for example,intrascleral delivery is somehow invasive,and episcleral delivery device needs to be made thin to prevent erosion of conjunctiva,iontophoresis needs to be frequently repeated as of its short-term effect.With the development of bio-material engineering technology,episcleral microfilm could become an ideal drug delivery route for posterior segment ocular diseases.

Vancomycin loaded gelatin/β-TCP composite porous scaffolds for the treatment of infected tibial bone defect in rabbit / 中华骨科杂志

Objective To confirm the vancomycin loaded gelatin/β-TCP composite porous scaffolds could be used as sustained-release system,and investigate its efficiency of eliminating infections and repairing bone defects for the treatment of infected bone defects in rabbit.Methods The biodegradable gelatin sponge containing different contents (0,10％,30％,50％) of β-tricalcium phosphate ceramic (β-TCP) was prepared for the controlled-release of vancomycin and labeled with G-0 TCP,G-10 TCP,G-30 TCP and G-50 TCP respectively.Examinations of scanning electron microscopy,porosity analyses and mechanical test were performed.The K-B method was used to investigate the controlled release of vancomycin.Chronic Methicillin-resistant Staphylococcus aureus osteomyelitis models of rabbit were established.After thorough debridement,the infected bone defects were treated in four different groups:blank control group,G-0 TCP group,G-10 TCP group,and G-30 TCP group.At 4 and 8 weeks after implantation,X-ray and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects.Results The prepared gelatin/β-TCP scaffold exhibited a homogeneously interconnected-3-D porous structure.And the β-TCP granules were localized evenly on the walls of the composite scaffold.There were no significant differences in the pore size of different scaffolds.However,the β-TCP granules can improve the interconnection.The porosity exhibited an obvious increase in G-10 TCP and G-30 TCP composite scaffolds compared with G-0 TCP scaffold.In contrast,too high content of β-TCP granules decreased the porosity.And the porosity exhibited an obvious reduction in the G-50 TCP composite scaffold.The compressive modulus of the vancomycin loaded scaffolds increased with the increase of the β-TCP amount.The scaffold G-0 TCP exhibited the longest duration of vancomycin release and the duration reached 8 weeks.With the increased content of β-TCP granules,the release duration shortened obviously.Compared with the G-50 TCP composite scaffold,the G-10 TCP and G-30 TCP composite scaffolds revealed a better controlled release of the drugs,and the total amount of the drugs was released within 7 weeks.However,the total amount of vancomycin released from the G-50 TCP composite scaffold lasted for 3 weeks.In the treatment of chronic MRSA osteomyelitis of rabbits,the G-30 TCP composite scaffold showed a better performance in the eliminating infections and bone defects repair.At 8 weeks after implantation,signs of osteomyelitis,including osteolysis,development of periosteal reactions,and sequestral bone formation were observed in the animals of blank control group.Signs of infection were absent in other treatment group.In the group treated with G-30 TCP composite scaffold,the bonedefects were repaired completely at 8 weeks after implantation.However,in the groups treated with G-0 TCP and G-10 TCP composite scaffold,the bone defects were not repaired.Conclusion The composite scaffolds could achieve local therapeutic drug levels over an extended duration.And the gelatin with 30％ β-TCP granules composite scaffold had optimal porosity,interconnection,mechanical properties and controlled release performances.It exhibited good performances in infection control and bone defect repair in the chronic MRSA osteomyelitis model.

Sustained-released mixture of vascular endothelial growth factor 165 and fibrin glue strengthens healing of ileal anastomoses in a rabbit model with intraperitoneal infection

PURPOSE: To investigate the effects of a sustained-released mixture of vascular endothelial growth factor 165 (VEGF165) and fibrin glue (FG) local administration on postoperative rabbit ileal anastomoses. METHODS: One hundred twenty-eight male and female New Zealand white rabbits underwent intraperitoneal infection subsequent ileal anastomosis surgery were divided randomly into 4 groups, including 32 animals in each, applied with saline solution, FG, rhVEGF165 and a mixture of rhVEGF165 with FG (VEGF + FG) on the anastomoses, respectively. The incidences of anastomotic leakage were observed. Histopathological examination for inflammatory infiltration, fibroblast proliferation, and capillary vascular proliferation were performed. Then, bursting pressure and hydroxyproline concentrations were assessed in anastomoses sits on postoperative days 3, 5, 7, and 14. RESULTS: Rabbits in VEGF + FG group had the lowest incidence of leakage (P < 0.05). Histological evaluations revealed that granulation tissue was formed on days 5 after anastomosis; fibroblast proliferation and capillary vascular proliferation were significantly increased on days 7 and 14 in VEGF + FG group. Furthermore, there was a statistically significant difference in the mean bursting pressures between VEGF + FG group and other groups on days 7 and 14 (P < 0.05), and rabbits in VEGF + FG group exhibited a higher concentration than VEGF group (P < 0.05) and FG group (P < 0.05) on day 14. CONCLUSION: Administration of VEGF165 mixed with FG to ileal anastomosis accelerates wound healing and enhances the anastomosis by increased angiogenesis.

Construction of vascular sustained release model of vascular endothelial growth factor / 中华胸心血管外科杂志

Objective To construct a model of small caliber vascular endothelial growth factor(VEGF) in tissue engineering,to investigate the performance of the sustained-release microspheres and vascular stent,and to provide materials and theoretical basis for animal experiment.Methods The sheep carotid arteries were treated with a cellular reagents,the cellular conditions and the stent properties were observed.Preparation of sustained release microspheres containing VEGF,particle size,encapsulation efficiency,drug loading and release curve were measured.The effective combination of the slow release microsphere and the vascular stent was used in the freeze drying technology.The rat vascular endothelial cells grown in tissue engineered blood vessel model release lumen,observe the growth of endothelial cells.Results After the treatment,the original performance of the vascular stent can be maintained.The average particle size of the microspheres was (9.8 ± 6.0) μm,which could be released slowly in 20 days,and the release rate was 70％.Microspheres can effectively with the tissue.engineering blood vessel tight binding.Rat vascular endothelial cells can grow in the vascular stent surface.Conclusion Using Triton X-100,DNA/RNA ribozyme for acellular reagent,stent performance is good.PLGA microspheres have good sustained release performance,and constructing appropriate tissue engineered small caliber vascular release model by using freeze drying technology can make the stent compact structure.

Preparation of RFP-loaded a novel polylactone/β-tricalcium phosphate composite scaffold / 中华骨科杂志

Objective To explore a biodegradable drug?loaded composite scaffold and determine its bone regeneration and local long?term drug release ability. Methods In this study, RFP?loaded a novel poly (caprolactone)?b?poly (lactide?co?gly?colide)/β?TCP composite scaffold was produced using particle?leaching/freeze?drying technique. And the obtained composite scaffold was characterized by SEM, TGA, UV spectrophotometer, universal testing machine and so on. New Zealand rabbits were used to prepare bone defects, which was treated by the implantation of active artificial bone loaded with or without RFP. The blank group was untreated. Then the repairing effects of the materials were examined. Results The obtained porous scaf?fold has inter?connected and uniformly distributed pores, and the diameters of pores range from 200 μm to 300 μm. Many mi?cropores (10 μm to 50 μm) can be observed on the wall of macropores. The total porosity of the porous composite scaffold can reach as high as 83.4%; the β?TCP content of the scaffolds is 51.2%. Meanwhile, the addition of β?TCP avoided volume shrinkage compared with b?PLGC scaffold; Additionally, the porous composite scaffold has good compressive strength ( 240 kPa) and compressive modulus (1.0 MPa); And the drug loading of the scaffold was 3.2%,which could smoothly release drug for 63 days after a period of burst release for a week. All defects in the experimental groups were radiographically repaired. There were significant differences between the experimental groups and the control group. Conclusion RFP?loaded poly (cap?rolactone)?b?poly (lactide?co?glycolide)/β?TCP composite scaffold is expected to benefit in drug therapy and bone repair in the treatment of bone tuberculosis.

Fabrication of the anti-tuberculosis controlled drug delivery system with Ti-PDA-PEG-PLGA-INH and investigation of the biological characteristics / 中华骨科杂志

Objective To fabricate an anti?tuberculosis controlled drug release coating with Ti?PDA?PEG?PLGA?INH and to investigate its surface characteristics, in vivo and in vitro drug release behavior, and tissue biocompatibility. Methods 4?arm?polyethylene glycol (PEG) was synthesized first. Then cover the surface of titanium (Ti) with a layer of poly dopamine (PDA) by Michael addition reaction. Use porous starch and 4?arm?PEG as a carrier, load with isoniazid (INH), then attach to the surface of titanium by casting or sol?gel dip coating methods, and then cover with a layer of poly lactic?co?glycolic acid (PLGA) by the same method, to fabricate the Ti?PDA?PEG?PLGA?INH composite coating finally. The functional group of 4?arm?PEG was charac?terized by proton nuclear resonance spectroscopy (HNMR). The surface characteristics of Ti?PDA?PEG?PLGA?INH were evaluated by scanning electron microscope (SEM), while drug release behaviors were detected by high performance liquid chromatography (HPLC) and the cumulative release rate was calculated, and carry out the antibacterial performance in vitro. The animal model of femoral condyle bone defect was established in 25 New Zealand white rabbits. Titanium rods covered with PDA?PEG?PLGA?INH coating were implanted into defect area. INH concentrations were detected by HPLC in venous blood, muscle and bone tissue at each time point postoperatively. Another 12 rabbits were randomly divided into experimental group and control group, the experi?mental group was implanted with titanium tablets and titanium rods coated with PDA?PEG?PLGA?INH in the paraspinous muscle and left femoral condyles respectively, while the control group was implanted with a blank sheet of titanium tablets and titanium rods in the same place. Hematoxylin and Eosin Staining were used to observe the biocompatibility of the composite system in vivo at 28 and 56 days postoperatively. Results Ti?PDA?PEG?PLGA?INH controlled drug release coating uniformly distributed on the surface of plates and rods, with translucent form and smooth surface. In vitro INH release kinetics exhibited a short?burst release during the first 8h, and the cumulative release of the INH was about 65%. On the 9th day, the cumulative release of the INH was about 90%, and then the release tended to be flat, and the drug release behavior in vitro continued more than 20d. In vivo release test showed that the concentration of INH in vein blood, muscle and bone tissue around the composite system was increased steadi?ly postoperatively. On about the 28th day, the concentration reached the max. However, the INH concentrations in muscle and bone tissue around the composite system were still higher than the minimum inhibitory concentration (MIC) on the 56th day. The antibacterial test in vitro showed that the titanium tablets coated with PDA?PEG?PLGA?INH formed obvious bacterial inhibition zones. The pathological results indicated that mild inflammatory reaction was seen in the 4th week postoperatively, and the reac?tive capsule formed with loose connective tissue. In the 8th week postoperatively, there's no obvious inflammation occurred, and the reactive capsule became more dense and thicker. Conclusion The study successfully fabricated the Ti?PDA?PEG?PLGA?INH anti?tuberculosis controlled drug release coating, with reasonable release behavior both in vivo and in vitro, effective antibac?terial effect of Mycobacterium tuberculosis in vitro and good tissue biocompatibility, which is a potentially effective drug delivery system for spinal tuberculosis.

An in vitro experimental study on the physical and elution properties of PMMA bone cement loaded with rifampicin, iso-niazid, pyrazinamide and moxifloxacin / 中华骨科杂志

Objective To investigate the feasibility of Antituberculotic?loaded bone cement (ATLBC) prepared by mix?ing the anti?TB drugs Rifampicin (RFP), Isoniazid (INH), Pyrazinamid (PZA), Moxifloxacin (MFX) with Palacos R PMMA bone cement in Total Joint Arthroplasty treatment for Joint Tuberculosis. Methods Forty grams of Palacos R bone cement powder without antibiotics was mixed with 1 or 2 grams of RFP, INH, PZA and MFX respectively. According to ISO 5833:2002 stan?dard, 8 groups of ATLBC standard test specimen were prepared as experiment group and Palacos R PMMA bone cement with?out antibiotics was prepared as control group. Physical properties (such as the average dough time, curing time, maximum tem?perature), mechanical strength (such as the compressive strength, the bending resistance strength, the modulus of elasticity) and the concentrations of eluant drug in different time points of ATLBC were detected. Results In RFP (1 g), RFP (2 g), INH (1 g) and INH (2 g) group, the average dough time and curing time were longer than those in control group, which exceeded the standard scope of ISO, while the average maximum temperature was significantly lower than that in control group. The INH ( 1 g) group and INH (2 g) group hardened after mixing for 14 days. The RFP (1 g) group and RFP (2 g) group hardened after mixing for 30 days. Twenty minutes after mixing and hardening, the compressive strength, bending resistance strength and modulus of elastic?ity were significantly lower than the specified values of ISO standard. The physical properties and mechanical strength in PZA ( 1 g) group, PZA (2 g) group, MFX (1 g) group, MFX (2 g) group and control group were in accordance with the specified values of ISO standard, and they hardened after 20 minutes. In RFP (1 g) group, RFP (2 g) group, INH (1 g) group, INH (2 g) group, PZA (1 g) group, PZA (2 g) group, MFX (1 g) group and MFX (2 g) group, the concentration of eluant could maintain for 3 days, 7 days, 90 days, 90 days, 45 days, 60 days, 60 days and 60 days respectively. Conclusion RFP and INH mixing with Palacos R PMMA bone cement can hinder the aggregation of bone cement so they are unsuitable for preparing ATLBC. PZA and MFX mixing with Palacos R PMMA bone cement do not affect the physical properties of bone cement, with excellent mechanical strength and elu?tion properties. Because the minimal inhibitory concentration of PZA is higher and its antimicrobial activity maintains shorter time, while MFX maintains longer time in antimicrobial activity, it's more suitable for the preparation of ATLBC.

Preparation of tamsulosin hydrochloride sustained-release pellets / 第二军医大学学报

Objective To prepare tamsulosin hydrochloride sustained-release pellet by coating with acrylic copolymers. Methods EUDRAGIT® NE 30 D was used as the main sustained-release material, EUDRAGIT® L 30 D-55 and Methocel® E3 were used as release adjust agent; a one layer sustained-release coating was done for tamsulosin hydrochloride-loaded pellet in bottom spray fluid bed. A three factor, three-level Box-Behnken design was used to optimize the percentages of EUDRAGIT® L 30 D-55 and Methocel® E3 in the total dry polymers and the weight gain of total dry polymers as the three nonlinear factors, which mainly influenced drug release of the pellets in the formula of sustained-release coating layer. In-vitro cumulative drug release after 2 h, 3 h and 5 h was tested and the following target range:2 h 12%-39%, 3 h 44%-70% and 5 h>70% were set for optimization. Results The formulation and process of one layer sustained-release coating, which was synergistically controlled by the three materials based on acrylic copolymers, was determined after optimization:the total dry polymers were applied with a weight gain of 12% on drug pellets, with EUDRAGIT® L 30 D-55 dry polymers and Methocel® E3 being 7% and 2% of the total dry polymers, respectively. The sustained-release pellets coated with the optimized formulation provided a release profile that was close to the predicted value and similar to that of the commercial product Harnal® capsule pellets by f2 similarity factor comparison (f2 values of three batches were 71,73 and 80). Conclusion The established formulation and process is a simple and reproducible method to prepare tamsulosin hydrochloride sustained-release pellets with good stability.

Pharmacological and Safety Profile of Dexlansoprazole: A New Proton Pump Inhibitor - Implications for Treatment of Gastroesophageal Reflux Disease in the Asia Pacific Region

Although gastroesophageal reflux disease is not as common in Asia as in western countries, the prevalence has increased substantially during the past decade. Gastroesophageal reflux disease is associated with considerable reductions in subjective well-being and work productivity, as well as increased healthcare use. Proton pump inhibitors (PPIs) are currently the most effective treatment for gastroesophageal reflux disease. However, there are limitations associated with these drugs in terms of partial and non-response. Dexlansoprazole is the first PPI with a dual delayed release formulation designed to provide 2 separate releases of medication to extend the duration of effective plasma drug concentration. Dexlansoprazole has been shown to be effective for healing of erosive esophagitis, and to improve subjective well-being by controlling 24-hour symptoms. Dexlansoprazole has also been shown to achieve good plasma concentration regardless of administration with food, providing flexible dosing. Studies in healthy volunteers showed no clinically important effects on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition, with no dose adjustment of clopidogrel necessary when coprescribed. This review discusses the role of the new generation PPI, dexlansoprazole, in the treatment of gastroesophageal reflux disease in Asia.

Preparation and performance of LID-MWCNT based sustained release targeted drug delivery system / 天津医药

Objective To prepare a targeted antitumor drug delivery system using large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) for sustained release and to study its performance. Methods LID-MWCNTs were puri?fied and oxidized,then use nanocarriers and USTs as homologous blockers. Folic acid and fluorescent labels were conjugat?ed onto the external surfaces of nanocarriers. CDDP (cisplatin) was encapsulated and ultrashort tubes (USTs) were employed to block the drug entry/exit paths. The microstructure of resulted drug delivery system (DDS) was observed, while drug load?ing efficiency and drug release profile in vitro were determined. The tumor-targeting property and cytotoxicity of DDS were also assessed. Results LID-MWCNT based sustained release targeted drug delivery system was established. Drug loading efficiency of CDDP@UST-FA-LID-MWCNTs was as high as 70.97%. A typical biphasic sustained release pattern was dem?onstrated, and the accumulating release time was 18 h. DDS exhibited a certain kind of tumor-targeting property, and inhibit?ed proliferation of tumor cells in a dose-dependent manner. Conclusion CDDP@UST-FA-LID-MWCNT drug delivery system exhibited an improved drug loading efficiency and a sustained drug release profile. It could specifically target the tu?mor cells and had a significant antitumor effect.

Preparation and sustained-release property of prednisolone implantable films / 中国组织工程研究

BACKGROUND:In recent years, the use of prednisolone has good achievements in functional recovery after peripheral nerve injury, but its short half-life, instable plasma concentrations and greater adverse reactions limit its clinical application. OBJECTIVE:To prepare prednisolone implantable films and to explore the sustained-release property of prednisolone implantable films. METHODS:Novel reverse micellar emulsion-solvent evaporation method was used to prepare nanoparticles which contains prednisolone, and we investigated the properties of prednisolone-loaded nanoparticles, including morphological form, diameter, drug loading, encapsulation efficiency, in vitro release properties. Then, composite film was prepared with the nanoparticles above and col agen, chitosan, soybean phosphatidylcholine. The properties of composite films, such as morphological form, the interaction among film materials, in vitro releasing curve, were investigated. RESULTS AND CONCLUSION:The prednisolone-loaded nanoparticles displayed favorable microstructure such as smooth surface, consistent diameters. The mean diameter of the nanoparticle was 500 nm and the max encapsulation efficiency of the nanoparticle was more than 90%. The nanoparticle displayed obvious sustained-release effect in vitro, but it exhibited a certain burst release phenomenon. We found that the nanoparticles were uniformly distributed inside and on the surface of the composite film;and the in vitro release rate of the film was slower and more stable than the nanoparticles. The composite film displayed favorable sustained-release effect with no burst release. From what we have il ustrated above, we can safely come to a conclusion that the prednisolone-loaded film possesses good sustained-release effects.

Research of the anti-infective and osteogenic effects of the infection-prevention tissue engineered bones on femoral large bone defects in goats / 中华骨科杂志

Objective To establish the anti-infective tissue engineered bones (TEBs) and evaluate the anti-infective and osteogenic effects of the infection-prevention TEBs on femoral large bone defects in goats.Methods Based on the controlledrelease antibiotic system fibrin gel-coated vancomycin alginate beads (FG-Vanco-AB),the infection-prevention TEBs were established and evaluated.They were transplanted into the critical-size defects in the right femurs of goats.TEBs without the controlled-release antibiotic system were used as controls and transplanted into the left femoral defects.The breakpoint sensitivity of vancomycin (5 mg/mL) for S.aureus was used as a standard concentration.Postoperatively,the vancomycin concentrations in the lesion site,in the adjacent site and in the circulation,as well as the anti-infective effects of the infection-prevention TEBs were evaluated by High-performance liquid chromatography (HPLC).Bone hcaling was assessed by histology,CT and ECT.The results were used to evaluate the osteogenic effect of the infection-prevention TEBs.Results Results from ESM,CLSM and in vivo tracing showed that the in vitro and in vivo survival conditions of seeded cells were analogous to those of TEBs.The effective concentration (over the bactericidal concentration) of vancomycin in bilateral defects and in blood lasted for 28 days,2 days and 7 days,respectively.The concentration of vancomycin in the femur decreased gradually from the grafted site to both ends.At 28 and 56 days postoperatively,the ECT results showed no significant difference between the right and left femurs.CT and histology demonstrated that at 14,28 and 112 days after surgery,bone defects in the bilateral femurs were repaired synchronously,and were completely covered by new bone tissue after 112 days.Conclusion The anti-infective TEBs were successfully established.FG-Vanco -AB in the transplanted sites provided the local bone tissues with anti-infective capability whilst not interfered the process of bone reconstnction and wound healing.

An preliminarily experimental study of bone mineral density mediated by new tuberculosis-controlled release composite / 中国医师杂志

Objective To investigate bone mineral density ( BMD ) after filling in the bone scaffolds with anti-tuberculosis controlled-release microspheres, and provide experimental basis for decrease of the side effects of anti-tuberculosis therapy after spinal surgery.Methods The bone densitometer was used to observe the changes of bone mineral density before and after the infusion with the artificial allograft bone (Group A), the controlled release complex of the RFP controlled-release microspheres-artificial allograft bone (Group B), and RFP-artificial allograft bone complex (Group C), respectively.Results BMDs of three groups before perfusion were not different significantly [Group A:(0.191 ±0.018)g/cm2;Group B:(0.186 ±0.016)g/cm2;Group C:(0.189 ±0.018)g/cm2;P >0.05].BMDs of three groups after perfusion were not different significantly [Group A:(0.191 ±0.018)g/cm2;Group B:(0.179 ±0.023)g/cm2;Group C:(0.185 ±0.021)g/cm2;P >0.05].Conclusions RFP microspheres using ultrasonic vibration method and the porous bone were prepared to controlled-release anti-tuberculosis complex .BMD of three groups after perfusion were not influenced obviously .

Preparation and characterization of recombinant human bone morphogenetic protein-2/poly lactic acid sustained release microspheres / 中国组织工程研究

BACKGROUND:Poly lactic acid as an excellent delivery has good biocompatibility. OBJECTIVE:To prepare recombinant human bone morphogenetic protein-2 (rhBMP-2)/poly lactic acid (PLA) sustained release microspheres, and to study its physical and chemical properties. METHODS:The rhBMP-2/PLA sustained release microspheres were prepared using w/o/w solvent evaporation method. Scanning electron microscopy, laser particle size, zeta potential, and swel ing properties were detected. ELISA kit was utilized for measurement of encapsulation efficiency, drug-loading rate and in vitro drug release rate. RESULTS AND CONCLUSION:Under the scanning electron microscope, rhBMP-2/PLA sustained release microspheres were approximately circle with excellent dispersion. The uniform spheres were visible with a mean particle size of 839.6 nm. The zeta potential were (-32.93±3.74) mV. The swel ing coefficient was 1.157±0.059. The drug-loading rate and encapsulation efficiency of rhBMP-2/PLA sustained release microspheres were (88.943±2.878)%and (0.026±0.001)%respectively. The drug release rate at 1 day was about 10.199%, then the drug release was relatively constant, and til 19 days, the cumulative drug release rate was 54.643%. These findings indicate that the constructed rhBMP-2/PLA sustained release microspheres meet the requirement of the Chinese Pharmacopoeia (10th edition) that the encapsulation efficiency is not less than 80%and the microspheres have a good slow-release function in vitro.

Preparation and characterization of ciliary neurotrophic factor sustained-release microcapsules / 中国组织工程研究

BACKGROUND:Conventional ophthalmic delivery of ciliary neurotrophic factor (CNTF) is extremely difficult to pass the blood-retinal barrier, resulting in a very low bioavailability and the need of long-term drug delivery. To solve the problem, the CNTF can be encapsulated in a semi-permeable membrane to form a microcapsule, which may then achieve the release of bioactive substances encapsulated, or bioactive molecules secreted by living cels and smal molecular metabolites through semi-permeability of the special membrane. OBJECTIVE:To prepare a special structural CNTF sustained-release microcapsule. METHODS: A selected poly(ether sulfone) holow fiber was cut into 1 cm long with its two ends sealed by 1181-M medical adhesive using UV curing. To prepare CNTF encapsulated microcapsule, one end was first sealed, and then the CNTF was loaded to poly(ether sulfone) microcapsule from the other end which then was sealed. The leaching liquor of sustained-release microcapsule was co-cultured with mouse fibroblast L929, to observe the cytotoxicity of the microcapsule. The sustained-release microcapsule was co-cultured with mouse retinal pigment epithelial cels, to observe the celladhesion ability of the microcapsule. The CNTF sustained-release microcapsule was immersed in physiological saline, to observe the degradability. Moreover,in vitro release behavior of immunoglobulin and CNTF were evaluated. RESULTS AND CONCLSION:The CNTF sustained-release microcapsule had an inner diameter of about 398 μm and a membrane thickness of about 145 μm. The microcapsule presents a lot of macropores in the outer wal and many 10 nanometers micropores in the inner wal. The sustained-release microcapsule was not degraded in saline within 4 months, indicating good cellcompatibility. The microcapsule can selectively release CNTF while protecting against invading of antibodies (IgG), showing its good selective permeability. Meanwhile, the sustained-release microcapsule improved the initial burst release of traditional drug delivery vesicles. The microcapsule presents a mild sudden release in the middle stage, and then a sustained release.

The sustained-release carrier of Nanosilver-epidermal growth factor in promoting wound healing of diabetes / 中国医师杂志

Objective To investigate the antibacterial properties and curative effects of a nanosilver-epidermal growth factor (NanoAg-EGF) sustained-release carrier.Methods First,in accordance with former method,sustained-release carrier of NanoAgEGF was prepared,with the design of the NanoAg-EGF group,NanoAg-alone group,EGF-alone group,control groups of normal saline-alone,and benzylpenicillin sodium.Contrasting detection on antibacterial properties of five kinds of common microbes (staphylococcus aureus,escherichia coli,pseudomonas aeruginosa,candida albicans,and streptococcus pneumonia) in each group was used to confirm their antibacterial properties.Then,wound models of diabetic rats were randomly divided into five groups,with the wound treatments by sustained-release cartier of NanoAg-EGF,combined application of NanoAg + EGF,EGF-alone,NanoAg-alone,and normal saline-alone control group,respectively.The observation on the healing situation of each group in different times was used to ensure the curative effect.Results In the antibacterial experiments,it was found that the NanoAg-EGF and NanoAg had strong antibacterial properties.Their antibacterial properties had no significant difference (P ＞ 0.05).The control group,penicillin sodium only had relatively weak antibacterial properties on staphylococcus aureus and streptococcus pneumoniae,with obviously weaker function compared to the NanoAg-EGF and NanoAg groups (P ＜ 0.05).The control groups,EGF-alone and normal saline-alone had no inhibitor function on each kind of pathogenic microorganisms.In the wound healing experiments on diabetic rats,it was found that NanoAgEGF shortened significantly the wound healing time of diabetic rats (P ＜ 0.05).On the 3rd day,the healing rate of each group had no difference (P ＞ 0.05).On the 7th day and 13th day,the healing rates of NanoAg-EGF [(61.71 ± 8.78)％ and (100 ± 2.60) ％] were significantly higher than the other four groups (P ＜ 0.05).Conclusions NanoAg-EGF not only has good antibacterial properties but also can promote rapidly the wound healing of diabetes.