Paclitaxel (PTX)-loaded self-assembling nano-micelles (PTX/NMs) were prepared based on amphiphilic cholesterol-bearing γ-polyglutamic acid (γ-PGA-graft-CH). The properties of PTX/NMs in vitro and in vivo were investigated. The results indicated that PTX could be entrapped in γ-PGA-graft-CH NMs. PTX/NMs was characterized with a size of (343.5 ± 7.3) nm, drug loading content of 26.9% ± 0.8% and entrapment efficiency of 88.6% ± 1.7% at the optimized drug/carrier ratio of 1/10, and showed a pH-sensitive sustainable drug-release and less cytotoxicity in vitro. In vivo release and the pharmacokinetics study in mice showed that the elimination half-life (t1/2β) and area under curve (AUC) of PTX/NMs were significantly higher than those of PTX/polyoxyethylene castor oil (PTX/PCO), and less clearance (CL) of PTX/NMs was also observed. PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a good tumor-inhibiting activity in tumor-bearing mice. This study would lay a foundation on the potential application of γ-PGA-graft-CH NMs were the antitumor drug-delivery.
Objective To investigate the biomechanical characteristics of Schatzker type Ⅱ tibial plateau fracture fixed by different bone grafting methods and internal fixations. Methods Twenty-four embalmed specimens of adult knee joint were selected to make Schatzker type Ⅱ tibial plateau fracture models, which were randomly divided into 8 groups (groups A1-D1 and groups A2-D2, n=3). After all the fracture models were restored, non-structural iliac crest bone grafts were implanted in group A1-D1, and structural iliac crest bone grafts in groups A2-D2. Following bone grafting, group A was fixed with a lateral golf locking plate, group B was fixed with lateral golf locking plate combined compression bolt, group C was fixed with lateral tibial “L”-shaped locking plate, and group D was fixed with lateral tibial “L”-shaped locking plate combined compression bolt. Compression and cyclic loading tests were performed on a biomechanical testing machine. A distal femur specimen or a 4-cm-diameter homemade bone cement ball were used as a pressure application mould for each group of models. The specimens were loaded with local compression at a rate of 10 N/s and the mechanical loads were recorded when the vertical displacement of the split bone block reached 2 mm. Then, compressive and cyclic loading tests were conducted on the fixed models of each group. The specimens were compression loaded to 100, 400, 700, and 1 000 N at a speed of 10 N/s to record the vertical displacement of the split bone block. The specimens were also subjected to cyclic loading at 5 Hz and 10 N/s within the ranges 100-300, 100-500, 100-700, and 100-1 000 N to record the vertical displacement of the split bone block at the end of the entire cyclic loading test. The specimens were subjected to cyclic loading tests and the vertical displacement of the split bone block was recorded at the end of the test. Results When the vertical displacement of the collapsed bone block reached 2 mm, the mechanical load of groups A2-D2 was significantly greater than that of groups A1-D1 (P<0.05). The mechanical load of groups B and D was significantly greater than that of group A under the two bone grafting methods (P<0.05); the local mechanical load of group D was significantly greater than that of groups B and C under the structural iliac crest bone grafts (P<0.05). There was no significant difference (P>0.05) in the vertical displacement of the split bone blocks between the two bone graft methods when the compressive load was 100, 400, 700 N and the cyclic load was 100-300, 100-500, 100-700 N in groups A-D. However, the vertical displacement of bone block in groups A1-D1 was significantly greater than that in groups A2-D2 (P<0.05) when the compression load was 1 000 N and the cyclic load was 100-1 000 N. The vertical displacement of bone block in group B was significantly smaller than that in group A, and that in group D was significantly smaller than that in group C under the same way of bone graft (P<0.05). Conclusion Compared with non-structural iliac crest bone grafts implantation, structural iliac crest bone grafts is more effective in preventing secondary collapse of Schatzker type Ⅱ tibial plateau fracture, and locking plate combined with compression bolt fixation can provide better articular surface support and resistance to axial compression, and the lateral tibial “L”-shaped locking plate can better highlight its advantages of ‘raft’ fixation and show better mechanical stability.