Objective To develop the plastic nano-hydroxyapatite (nano-HA)/poly (3-hydroxybutyrate-hydroxyvalerate) polyethylene glycol(PHBV-PEG) gentamicin (GM) drug delivery system(DDS)(nano-HA/PHBV-PEG-GM-DDS) for treating osteomyelitis and find its releasing character in vivo. Methods The plastic nano-HA/PHBV- PEG-GM-DDS was prepared using nanoHAas the core carrier of GM, nano-HA with PHBV and PEG as coating and plastic fibrin glue(FG) as microsphere scaffold. The morphological features of nano-HA,drug loaded nano-HA and drug loaded nano-HA/PHBVPEG microsphere were examined by electron microscope.The GM concentration in blood, cortex bone and cancellousbone was detected at 12 different time points by the method of K-B after the plastic nano-HA/PHBV-PEGGM-DDS was implanted into the femora of 36 rabbits. Its GM releasing character was assayed in vivo. Results Nano-HA was similar to a blackjack, and its length was less than 60 nm. Drug loaded nano-HA appeared natural crystal condensate, of which surface adsorbed massive GM. The average grain diameter was 200.5 nm. Drug loaded nanoHA/PHBV-PEG microsphere had a shrinkable porous structure, of which surface configuration was consistent. The average grain diameter was 34.5 μm. The GM concentration and the antibacterial annulus was in the linear correlation. The correlation coefficient was 0.998. In cortex and cancellous bone tissue, the GM concentration was about 95.50±16.50 μg/ml and 80.20±13.80 μg/ml from the plastic nano-HA/PHBV-PEG-GM-DDS on the 1st day, then decreased gradually. After 56 days of operation, the GM concentration still exceeded the minimum inhibitory concentrationfor the staphylococcus aureus, but the peak level of serum GM concentration wasunder the nephrotoxicity concentration. Conclusion Plastic nano-HA/PHBV-PEG-GM-DDS was a good drug delivery system with sustained antibiotic effect in vivo. It was an effective method for the treatment of osteomyelitis.
【Abstract】 Objective To introduce a new method using calcium phosphate cement/Danshen drug del ivery systemfor avascular necrosis of femoral head and to evaluate its cl inical outcome. Methods From May 2000 to June 2005, 48 patients (54 hips) with avascular necrosis of femoral head were treated with calcium phosphate cement/Danshen drug del ivery system implantation in the involved femoral head. There were 32 males(36 hips) and 16 females(18 hips) with an average age of 38.7 years (26-62 years). Twenty-one cases had the history of drinking or smoking, 15 cases had the history of receiving hormonotherapy and 2 had the history of injury in hip joint. The disease course was 2-32 months. According to standard of Association Research Circulation Osseous (ARCO) staging, 9 hips were classified as stage I, 31 as stage II and 14 as stage III. The operation consisted of removal of necrotic bone under weight-loading cartilage and the implantation of calcium phosphate cement/Danshen drug del ivery system, all mani pulations were done through a bone tunnel in trochanter. The function of hi p joint were evaluated and X-ray films were taken pre- and post-operatively. Results No phlebothrombosis of leg and foreign body action occurred in all cases, and incision healed by first intention. The postoperative follow-up averaged 42.5 months, ranging from 22 to 73 months. According to the evaluation criterion of Dandong 1995 for adult avascular necrosis of femoral head, the results were excellent in 33 hi ps, good in 17, fair in 3 and poor in 1, the excellent and good rate was92.6 %. Conclusion This method is relatively simple with less invasion, it not only improves the microcirculation of femoral head by local appl ication of traditional Chinese medicine, but also provide mechanic buttress in the weight-loaded area, which is beneficial to repair and reconstruction of femoral head. It may be a choice of minimally invasion surgery for femoral head necrosis.
ObjectiveTo investigate the expression of amniotic fluid levels and blood serum levels of matrix metalloproteinases-8 (MMP-8) and interleukin-6 (IL-6) in women with preterm delivery. MethodsBetween January 2010 and December 2012, we collected the amniotic fluid of 102 preterm pregnant women and 98 full term pregnant women and analyzed the MMP-8 levels and IL-6 levels in amniotic fluid and blood serum. Meanwhile, we also collected the amniotic fluid to do bacterial culture. ResultsThe amniotic fluid levels of MMP-8 in preterm pregnant women were higher than those in full term pregnant women [(320.45±59.88) vs (153.72±29.12) ng/mL, P<0.05], but there was no obvious discrepancy in the blood serum levels of MMP-8 in the two groups [(9.56±2.11) vs (9.42±2.01) ng/mL, P>0.05]. Both amniotic fluid levels and blood serum levels of IL-6 in preterm pregnant women were significantly higher than the full term pregnant women [(90.5±16.3] vs (20.6±12.5) μg/L, P<0.05; (159.2±20.4) vs (22.3±11.8) μg/L, P<0.05]. The positive bacterial culture rate of preterm pregnant women was higher than the full term pregnant women (8.8% vs 1.0%, P<0.05). ConclusionInfection is the most important reason for preterm pregnancy. MMP-8 level increases in the amniotic fluid, and the level of IL-6 in amniotic fluid and blood serum is a valuable clinical index for identifying premature delivery.
An clinical and pharmacokinetic study for a drug delivery system (DDS) of gentamycin-loaded chitosan bar were carried out with the purpose to evaluate its efficacy and giving further data for its clinical applications. Eighteen cases of chronic osteomyelitis were treated by surgical necrectomy with implantation of gentamycin-load chitosan bar in the prepared bone cavity. After operation, the concentration of gentamycin in serum and wound drainage fluid were examined at different times and blood urea nitrogen (BUN) and serum creatinine (Cr) as well. The clinical results were evaluated by the conditions of wound healing and clinical and roentgenographic manifestations. The results showed that the serum gentamycin concentration reached its peak level (0.86 microgram/ml) at 24 hours after operation and lasted for 4 days. No increase in the concentrations of BUN and Cr were observed after implantation. The gentamycin concentration in wound drainage fluid was several hundred times higher than the minimum inhibitory concentration (MIC) for staphylococcus aureus. All of the 18 cases were followed up for 24.8 months (in an range of 6-34 months) 16 patients received initial cure and without any recurrence. So, it could be concluded that the gentamycin-loaded chitosan DDS was a simple and effective method for the treatment of chronic osteomylitis without the necessity to carry out a second operation to remove the drug carrier, and it was sound to popularize its clinical application.
OBJECTIVE To manufacture adriamycin-porous tricalcium phosphate (A-PTCP) ceramic drug delivery system (DDS) as a possible method for bone defect treatment after bone tumor operation. METHODS A-PTCP DDS was made from putting adriamycin into PTCP. Thirty rabbits were divided randomly into group A(24 rabbits) and group B(6 rabbits). A-PTCP was implanted in the greater trochanter of the right femur in group A. Adriamycin were injected into veins in group B. Muscle around A-PTCP and plasma were taken out at different period. Adriamycin concentrations in muscle and plasma were measured by high performance liquid chromatography (HPLC). RESULTS A-PTCP could gradually release adriamycin over 10 weeks. Adriamycin concentrations in the muscle were higher than that in plasma. CONCLUSION A-PTCP may be a new method for repairing bone defects after bone tumor operation.
ObjectiveTo evaluate the therapeutic effect of liver transplantation (LT) combined with adenovirus-mediated delivery of herpes simplex virus thymidine kinase / ganciclovir (ADV-TK/GCV) in treatment of patients with hepatocellular carcinoma (HCC), so as to benefit more patients with HCC beyond the Milan criteria. MethodsThe clinicopathologic data of patients with HCC underwent LT by the author team since 2007 were collected and analyzed. The patients were assigned into simple LT group and LT+ADV-TK/GCV group. The 5-year cumulative overall survival rate and relapse free survival rate of all LT patients and the patients with LT beyond the Milan criteria by simple LT and LT+ADV-TK/GCV therapy were compared. Meanwhile, Cox regression was used to analyze the risk factors affecting long-term overall survival rate and relapse free survival rate of all patients with HCC after LT. ResultsA total of 216 patients eligible for inclusion were collected in this study, including 134 patients in the simple LT group and 82 patients in the LT+ADV-TK/GCV group, 162 of whom beyond the Milan criteria, including 101 patients underwent the simple LT and 61 patients underwent the LT+ADV-TK/GCV. There were no statistical differences in the baseline data between the simple LT and LT+ADV-TK/GCV in all patients and patients beyond the Milan criteria (P>0.05). There were no statistical differences in 5-year overall survival rate and relapse free survival rate of all patients with HCC (P>0.05). The 5-year cumulative overall survival rate of the LT+ADV-TK/GCV group was better than that of the simple LT group in the patients beyond the Milan criteria (χ2=4.11, P=0.047), but it was not found that the 5-year cumulative relapse free survival rate had statistical difference (27-month survival time as the critical value, P=0.46, P=0.06). Cox regression multivariate analysis results showed that the larger cumulative tumor diameter, the preoperative elevated serum alpha fetoprotein (>400 μg/L), later TNM stage, and without combination of ADV-TK/GCV therapy increased the probability of shorter overall survival of patients after LT; and the patient’s older age, the larger cumulative tumor diameter, and later TNM stage increased the probability of shorter relapse free survival after LT, and it was not found that the combination of ADV-TK/GCV therapy had an impact on the relapse free survival. ConclusionLT combined with ADV-TK/GCV therapy can obviously improve overall survival among patients beyond the Milan criteria, more patients with advanced HCC will be candidates for LT combined with ADV-TK/GCV therapy.
ObjectiveTo summarize the recent progress of the controlled releasing delivery of biological factors for cartilage repair. MethodsThe recently published 1iterature at home and abroad on the controlled releasing delivery of biological factors for cartilage repair was reviewed and summarized. ResultsVarious biological factors have been applied for repairing cartilage. For better cartilage repair effects, controlled releasing delivery of biological factors can be applied by means of combining biological factors with degradable biomaterials, or by micro- and nano-particles. Meanwhile, multiple biologic delivery and temporally controlled delivery are also inevitable choices. ConclusionAlthough lots of unsolved problems exist, the controlled releasing delivery of biological factors has been a research focus for cartilage repair because of the controllability and delicacy.
Parathyroid hormone (PTH) exerts multiple effects such as regulating bone remodeling, promoting angiogenesis, etc., and it is an active factor with great application potential for bone repair. In recent years, with the development of scaffold material loading strategies and parathyroid hormone-related peptides (PTHrPs), in situ loading of PTH or PTHrPs on scaffold materials to promote bone defect healing gradually becomes possible. Based on the current status and challenges of intermittent PTH (iPTH) for bone tissue engineering, the review summarizes the in-situ application strategies of PTH and the construction of PTHrPs as well as current problems and further directions in this field, with a view to propel the clinical application of scaffold materials loaded with PTH or PTHrPs in situ.
ObjectiveTo review the related studies on the application of nanomaterials in the treatment of osteomyelitis, and to provide new ideas for the research and clinical treatment of osteomyelitis.MethodsThe literature about the treatment of osteomyelitis with nanomaterials at home and abroad in recent years was reviewed and analyzed.ResultsAt present, surgical treatment and antibiotic application are the main treatment options for osteomyelitis. But there are many defects such as antibiotic resistance, residual bone defect, and low effective concentration of local drugs. The application of nanomaterials can make up for the above defects. In recent years, nanomaterials play an important role in the treatment of osteomyelitis by filling bone defects, establishing local drug delivery system, and self-antibacterial properties.ConclusionIt will provide a new idea and an important research direction for the treatment of osteomyelitis to fully study the related characteristics of nanomaterials and select beneficial materials to make drug delivery system or substitute drugs.
The suprachoroidal space is a potential space between the sclera and choroid. Suprachoroidal spacedrug delivery is becoming an applicable method to the ocular posterior segment diseases. Because it targets the choroid, retinal pigment epithelium and retina with high bioavailability and safety, while maintaining low levels elsewhere in the eye. In recent years, new discoveries has been carried out in different areas of interest, such as drug delivery methods, pharmacokinetics and clinical trials. Clinical trials with suprachoroidal space injection of triamcinolone acetonide are executed with promising findings for patients with noninfectious uveitis and diabetic macular edema. Suprachoroidal space triamcinolone acetonide injectable suspension is the first and currently the only agent specifically approved for uveitic macular edema by Food and Drug Administration. Nowadays, many clinical trails with suprachoroidal space drug delivery have been explored, although there are still many risks and uncertainties. With the development of technology in the future, suprachoroidal space drug delivery appears to be a promising treatment modality for ocular posterior segment diseases.