Background: Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The poor response to antitubercular agents necessitates the long-term use of high drug doses, resulting in low patient compliance, which is the main reason for chemotherapy failure and contributes to the development of multidrug-resistant TB. Patient non-compliance has been a major obstacle in the successful management of TB. The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency. Methods: RPT-loaded PLGA and PLGA-PEG NPs were prepared using premix membrane homogenisation combined with solvent evaporation method. The resulting NPs were characterised in terms of physicochemical characteristics, toxicity, cellular uptake and antitubercular activity. NPs were further evaluated for pharmacokinetic and biodistribution studies in mice. Results: The resulting NPs showed suitable and safe physicochemical characteristics and could be taken up by macrophages. RPT-loaded NPs were more effective against Mycobacterium tuberculosis than free RPT. In vivo studies revealed that NPs could improve pharmacokinetic parameters, particularly for RPT/PLGA-PEG NPs. Moreover, both formulations had no toxicity to the organs of mice and could reduce hepatotoxicity. Conclusion: The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency.
Spinal hydatid disease is rare and remains a serious health problem associated with high rates of recurrence. We report our experience in treating patients with thoracic spinal hydatidosis through a single-center case-series study. Methods: Sixteen patients with thoracic spinal hydatidosis were treated in our center between 1995 and 2017. A total en bloc spondylectomy (TES) was performed in three patients. Five patients were treated with posterior decompression and stabilization after removing the involved elements. The remaining patients underwent curettage and resection of the infected bone. The therapy was completed with medical treatment or radiotherapy. Results: Of the 16 patients, seven were men and nine were women; their mean age was 38.5 years (range 28-60 years). The infected area was the upper thoracic level in one patient, mid thoracic level in eight patients, and lower thoracic level in seven patients. Four patients had paraplegia and seven had paraparesis before surgery. At the last follow-up, five patients had successfully recovered from the neurological damage. During a mean follow-up of 4.75 years (range 2-12 years), eight patients had local recurrence; however, no patient who underwent TES had recurrence. Conclusions: An individualized surgical strategy should be decided carefully for each patient in the first intervention. In the early stages of the disease, TES should be considered as a treatment for suitable cases of primary thoracic spinal hydatidosis.
Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs).Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice.Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC–PLGA–PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 μg/mL, whereas this of free rifapentine was 0.25 μg/mL.Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.
ObjectiveThe purpose of this study was to investigate the clinical efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) for lumbar spinal stenosis (LSS).MethodsPatients who underwent UBE-TLIF due to single-segment LSS between August 2019 and July 2021 were retrospectively included in the study. Clinical outcomes evaluated include operative time, estimated blood loss (including postoperative drainage), time to ambulation, postoperative hospital stay, complications, visual analog scale (VAS) scores of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), and modified Macnab criteria. Interbody bony fusion at the index level was assessed using Bridwell grading criteria.ResultsA total of 73 patients (29 males and 44 females) were enrolled in this study. All surgeries were successfully performed without intraoperative conversion to open surgery. Magnetic resonance imaging (MRI) revealed optimal direct neural decompression after UBE-TLIF. The mean operative time was 150.89 ± 15.58 min. The mean estimated blood loss was 126.03 ± 17.85 ml (postoperative drainage was 34.84 ± 8.31 ml). Time to ambulation was 2.0 ± 0.75 days after the procedure. Postoperatively, the mean hospital stay was 5.96 ± 1.38 days. VAS scores of low back pain and leg pain, JOA, and ODI were significantly improved postoperatively compared with those before the operation, and differences were statistically significant (P < 0.05). Excellent and good outcomes were reported by 87.67% of patients according to the modified Macnab criteria at the final follow-up. A total of nine perioperative complications occurred, with an incidence of 12.33%. X-ray or computerized tomography (CT) 6 months after the procedure showed that 37 cases (50.68%) presented with segmental fusion, 30 cases (41.10%) showed incomplete fusion, and 6 cases (8.22%) showed no signs of fusion. However, bony fusion was achieved in all cases at the final follow-up.ConclusionsUBE-TLIF for LSS has the advantages of less surgical invasiveness and fast postoperative recovery.
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