【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.
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.
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.
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 observe the distribution and concentration of 125I-nerve growth factor (NGF) in rabbitsprime; eyes after intravitreal injection and posterior juxtascleral injection.Methods Intravitreal injection(group A) and posterior juxtascleral injection (group B) were performed with the dosage of 30mu;g/100mu;l 125I-NGF on left and right eyes in 45 white rabbits respectively. The gamma;-counts and the concentration of 125I-NGF (％ID/g) of each ocular tissue was determined 15 and 30 minutes, and 1,3,6,12,24,and 48 hours after injection. Results The 125I-NGF diffusion in group A was faster in ocular content and ocular inner wall. The vitreous content of 125I-NGF decreased gradually in group A, the curve changes in other eye tissues were normal. The concentration of 125I-NGF reached the peak 3 hours after injection in aqueous humor, iris and ciliary body, retina, and choroids, but 6 hours after injection in sclera and 8 hours in cornea. The changes of concentration of 125I-NGF in group B showed normal curve change. The peak time in group B were all 6 hours in all the tissues except aqueous humor (3 hours). Except the high concentration in vitreous body caused by intravitreal injection, the concentration of 125I-NGF in retina was the highest in group A. Conclusion Intravitreal injection of 125I-NGF can gain higher concentration in each ocular tissue than posterior juxtascleral injection, especially in retina. So intravitreal injection of NGF is a better ocular delivery method to treat the ocular fundus diseases.
Objective To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO). Methods This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n=129) or sham procedure (n=130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography. Results Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (P＜0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 34.9%, sham: 11.5%; mean BCVA change from baseline was DEX: 10.6±10.4 letters, sham: 1.7±12.3 letters; and mean CRT change from baseline was DEX: −407±212 μm, sham: −62±224 μm (all P＜0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was in-creased intraocular pressure (IOP). Increase sin IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery. Conclusions DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3 - 4 months after a single implant.