Cefquinome-loaded microsphere formulations against Klebsiella pneumonia infection during experimental infections

The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7?mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8?±?3.6?μm). The encapsulation efficiency and drug loading of cefquinome were 91.6?±?2.6% and 18.7?±?1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1β and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.     

Controlled release of celecoxib inhibits inflammation,bone cysts and osteophyte formation in a preclinical model of osteoarthritis

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n?=?6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39?mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6?days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

Nanofiber technology in the ex vivo expansion of cord blood-derived hematopoietic stem cells

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.     

星点设计-效应面法优化壳聚糖微球对凝血酶的固定化作用研究

目的 考察壳聚糖微球对凝血酶的固定化作用。方法 本研究以壳聚糖微球为载体,以戊二醛为交联剂将凝血酶固定于空白微球上,以固定化凝血酶的活性回收率为指标,采用星点设计-效应面法优化固定凝血酶的条件。结果 试验结果表明,壳聚糖微球固定凝血酶的最优条件是：凝血酶浓度69.32 U·mL^-1、戊二醛浓度0.18%、固定化时间1.88 h、固定化pH 7.08,凝血酶的活性回收率为81.55 %。结论 壳聚糖微球对凝血酶的固定化效果良好。     

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles

Background

Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.

Results

PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.

Conclusion

PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.     

庆大霉素-藻酸钙三维缓释微球的药物释放研究

目的研制庆大霉素一藻酸钙三维缓释微球并调控其庆大霉素的释放。使其达到长期局部抗菌的效果。方法制作不同浓度T、S、U组庆大霉素-藻酸钙缓释凝珠,与庆大霉素-骨水泥颗粒Y组进行庆大霉索释放情况比较。通过不同时间点抽取浸泡液,送紫外分光光度法（UV）及金黄色葡萄球菌（SA）培养检测,由此计算出各组包封率、释放率,绘制庆大霉素释放曲线。结果4组样品（微生物法）的包封率及30d药物释放率分别为：U组（53．99％、36．31％）,S组（39．62％、27．55％）。T组（34．20％、30．83％）,Y组（100．00％、48．49％）。U组的包封率较高,30d释放庆大霉素的总量较大,更接近Y组。4组间差异有统计学意义（P〈0．01）。U、Y组庆大霉素的释放明显高于S、T组的释放。各组30d内庆大霉素的浓度几乎都能超过金黄色葡萄球菌的最低抑菌浓度（MIC）．即〉2μg／mI。结论U组载药缓释凝珠30d内的庆大霉索释放较为理想。可作为BMSCs的三维培养支架。     

微球内部结构对体外释放的影响初步研究

目的 考察微球内部结构对其体外释放是否存在影响。方法 内水相中加入Na Cl-BSA比例不同的氯化钠,将微球切片考察其内部结构差异,通过摄取实验考察微球孔洞连通情况;研究不同处方体外释放曲线,并采用扫描电镜对释放过程不同时间点微球外观变化进行观察。结果 内水相中加入氯化钠后,微球内部结构有明显差异。微球内部结构会影响其体外释放曲线,且不同处方微球释放过程形态差异较大。结论 微球内部结构会显著影响其体外释放速率。     

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model

IntroductionPostoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging.ObjectiveThe goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor.MethodsVideoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement.ResultsThe presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection.ConclusionA prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.