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.
Objective To find out an effective technique torepair large segmental infected bony defect.Methods Calcium phosphate cement(CPC) incorporated with bone morphogenetic protein and gentamycin was embedded in the massive reconstituted bovine xenograft(MRBX), then CPC-MRBX was obtained after CPC’s solidification. In vivo test was applied to test the drug delivery capability of CPC-MRBX, in which it was implanted in the dorsal muscle pouch of 18 rabbits. The drug concentration of animal blood and surrounding soft tissue of the CPC-MRBX in the muscle pouch was measured 1, 2, 5, 10, 15, 20, 25, 30 and 35 d after operation, 2 rabbits each time. Large segmental infected femur defect in the rabbit model was created to test the repairing capability of CPC-MRBX. External fixation was done 1.5~2.0 cm above the knee, the most adjacent nail to fracture site was 0.5～0.8 cm away, and proper pressure was applied to the graft. In experimental group(n=25), the bony defect was replaced by CPC-MRBX, while in the control group(n=15) dissected bone block was re-implanted in original position. The animal was subjected to radiographic, histological examination at 4, 8, 16 and 24 weeks. The general condition was observed after the operation.Results CPC-MRBX was easily made under normal temperature and pressure. In viro drug delivery test showed that the drug concentration of the tissue remainedabove the minimal inhibitory concentration of staphylococcus 30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPC-MRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture. Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPCMRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture.Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.
Objective To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly-L-lysine (ε-PLL) and cyclodextrin (CD) (ε-PLL-CD-LZD), aiming to enhance antibiotic bioavailability, effectively penetrate and disrupt biofilm structures, and thereby improve the treatment of bone and joint infections. Methods ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. In vitro biocompatibility was evaluated through live/dead cell staining after co-culturing with mouse embryonic osteoblast precursor cells (MC3T3-E1), human umbilical vein endothelial cells, and mouse embryonic fibroblast cells (3T3-L1). The biofilm-enrichment capacity of ε-PLL-CD-LZD was assessed using Staphylococcus aureus biofilms through enrichment studies. Its biofilm eradication efficacy was investigated via minimum inhibitory concentration (MIC) determination, scanning electron microscopy, and live/dead bacterial staining. A bone and joint infection model in male Sprague-Dawley rats was established to validate the antibacterial effects of ε-PLL-CD-LZD. Results In ε-PLL-CD-LZD, the average grafting rate of CD reached 9.88%. The cell viability exceeded 90% after co-culturing with three types cells. The strong biofilm enrichment capability was observed with a MIC of 2 mg/L. Scanning electron microscopy observations revealed the effective disruption of biofilm structure, indicating potent biofilm eradication capacity. In vivo rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site (P<0.05). ConclusionThe ε-PLL-CD antibiotic delivery system provides a treatment strategy for bone and joint infections with high clinical translational significance. By effectively enhancing antibiotic bioavailability, penetrating, and disrupting biofilms, it demonstrated significant anti-infection effects in animal models.
Diabetes and its complications pose a serious threat to human life and health. It has become a public health problem of wide concern worldwide. Currently, diabetes is mainly treated with insulin injection in clinic. However, manual insulin injection still has many shortcomings. In recent years, with the deepening of research, it has been found that an automated insulin delivery system (AID), which combines a continuous glucose monitoring device with an insulin pump, can significantly improve the effectiveness of diabetes treatment and reduce the incidence of complications in patients. This paper firstly introduces the composition of the AID system and its working principle, and then details the development history and current status of the related technologies from the aspects of continuous glucose monitoring technology, insulin pumps and the development of closed-loop control algorithms, etc. Finally, this paper looks forward to the application prospect and future development of AID system in the field of diabetes treatment, providing theoretical reference for further research.
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.
Clinically, fracture nonunion often leads to pain and disability in patients. Fracture nonunion often requires additional surgery to restore skeletal muscle function, so the treatment of fracture nonunion has always been a difficult point in the field of orthopedics. In recent years, with the development of genetic engineering, the technology of using gene to treat fracture nonunion has been widely studied. A large number of experiments have confirmed that the target genes encoding growth factors related to fracture healing are introduced into target cells through different delivery methods in vivo or in vitro, thereby expressing specific growth factors can promote fracture healing, which provides a new way for treating fracture nonunion. This article will discuss the research status of different delivery methods of osteogenic genes, as well as their advantages and disadvantages, in order to provide a theoretical basis for targeted gene therapy for fracture nonunion.
Objective To investigate the physicochemicalproperties of the calcium phosphate cement (CPC) containing Danshen composite injection and its drug release rate. Methods This experiment included 4 groups and each group contained 6 specimens. CPC (2 g) was mixed with the setting solution that served as thecontrol group; 0.1,0.5 and 1.0 ml of Danshen composites injection (concentration, 1 000 mg/ml; pH, 7.35) were respectively added to CPC (2 g), which were used as the experimental groups 1, 2 and 3. The resulting specimens were investigated by the X-ray diffraction (XRD), the fourier transformed infrared spectroscopy(FTIR), and the scanning electron microscope (SEM).ResultsThe XRD analysis showed that the control group had a typical diffraction pattern of the hydroxypatite (HAP), which was consistent with the standard patternof HAP. When more Danshen was added in the experimental groups, the diffractionpeaks of HAP gradually decreased; when the diffraction angle 2θ was about 25.92°, the HAP peaks disappeared. Based on the FTIR analysis, with an increase of the drug concentration, the absorption peak of the hydroxy groups decreased. The SEM showed that the size of the CPC particle was related to the drug concentration; with an increase of the drug concentration, the CPC particle increased in number, resulting in an increasing trend of coacervation. The elution test showed that the drugrelease rate and capacity varied with the different concentrationsof Danshen. The initial release rate was relatively great, but after 96 hours the rate slowed down, lasting for a long time. Conclusion The physicochemical properties of CPC do not change when a proper dose (0.1 ml/2 g) of Danshen isadded to CPC. The Danshen composite can be effectively released from CPC, and so CPCcan be used as an ideal drugdelivery carrier for Danshen composite.
With the development of molecular and cellar cardiology, gene therapy to cardiovascular disease has become the hot spot and the direction of study. Now, preclinical studies on ultrasound-mediated gene delivery (UMGD) in cardiovascular disease have achieved some success, but it is still hindered by a series of practical challenges for clinical translation. Even so, UMGD still holds the promise to cardiovascular disease in gene therapy for its non-invasiveness, accuracy, safety and ability to deliver multiple genes with repeated deliveries. In this review, we will focus on the basic principle, the current development, the future prospect and drawbacks of UMGD in the therapeutic applications of cardiovascular disease.
Objectives To systematically review the efficacy and safety of carbetocinversusoxytocin on the prevention of postpartum hemorrhage (PPH) for women undergoing vaginal delivery. Methods PubMed, The Cochrane Library, Web of Science, CBM, WanFang Data, CNKI and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on carbetocinversusoxytocin on the prevention of PPH for women undergoing vaginal delivery from inception to January 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 and Stata 12.0 software. Results A total of 16 RCTs including 2 537 patients were included. The results of meta-analysis showed that: compared to oxytocin, carbetocin could reduce the amount of blood loss within 24h (MD=–107.68, 95%CI–130.21 to –85.15, P<0.000 01) and 2h (MD=–85.98, 95%CI–93.37 to –78.59,P<0.000 01), hemoglobin (Hb) within 24h after delivery (MD=–5.63, 95%CI–6.82 to –4.43,P<0.000 01), the occurrence of PPH (RR=0.46, 95%CI 0.32 to 0.66,P<0.000 01) and the requirement for additional uterotonic agents (RR=0.63, 95%CI 0.48 to 0.84,P=0.002). There was no significant difference in the risk of adverse effects between two groups. Conclusions Current evidence shows that carbetocin is superior to oxytocin in the prevention of PPH for women undergoing vaginal delivery, without increasing the adverse effects. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above the conclusion.