The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)- b-poly(lactide- co-glycolide)/poly(ε-caprolactone) (mPEG- b-PLGA/PCL) micelles were developed for encapsulation of DSF by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed. DSF is encapsulated within the core and the reservoir is stabilized by the hydrophilic shell to prevent rapid diffusion of DSF from the core. The DSF mixed micelles (DSF-MMs) showed good drug loading (5.90%) and a well-controlled particle size (86.4 ± 13.2 nm). The mixed micelles efficiently protected DSF from degradation in plasma, with 58% remaining after 48 h, while almost 90% of DSF was degraded after the same period for the DSF solution (DSF-sol), which was used as a control. The pharmacokinetics study showed that the maximum plasma concentration and bioavailability of DSF were improved by using the DSF-MMs (2 and 2.5 times that of the DSF-sol). The TIRs (tumor inhibition rates) of 5-FU, DSF-sol, and DSF-MMs were 63.46, 19.57, and 69.98%, respectively, implying that DSF-MMs slowed the growth of a H22 xenograft tumor model effectively.
Objective
The aim of this study is to analyze the microbiological characteristics of diabetic foot ulcer (DFU) and drug resistance of multidrug-resistant organisms (MDROs) and to reveal the potential risk factors for MDROs. This provides a basis for early empiric antibiotic treatment.
Methods
This study included 348 patients with diabetic foot ulcer in Chu Hsien-I Memorial Hospital & Metabolic Disease Hospital of Tianjin Medical University between May 2020 and November 2021. A total of 475 strains of bacteria were cultured, among which 240 strains were multidrug-resistant bacteria, accounting for 51%. Binary logistic regression was used to analyze risk factors. First, univariate analysis was used to calculate the
p
value of variables, and then multivariate analysis was conducted for variables with
p
< 0.1 to analyze independent risk factors. Risk factors with
p
< 0.05 in multivariable analysis were considered as independent risk factors. The strength of the association was represented by odds ratio and 95% confidence interval.
Results
Univariable logistic regression analysis demonstrated that previous hospitalization, previous antibiotic therapy, ulcer size >4cm
2
, surgical therapy, D-dimer, and CRP were associated with MDRO infection in patients with DFU. Multivariate logistic regression analysis demonstrated that previous hospitalization (OR = 1.91; 95% CI = 1.11–3.28;
p
= 0.02), ulcer size >4cm
2
(OR = 1.68; 95% CI = 1.03–2.76;
p
= 0.04), surgical therapy (OR = 2.14; 95% CI = 1.03–4.47;
p
= 0.04), and CRP (OR = 1.01; 95% CI = 1.00–1.01;
p
= 0.03) were independent risk factors for MDROs infection in diabetic foot patients. Drug resistance analysis may indicate that the proportion and drug resistance rate of
Acinetobacter baumannii
in Tianjin, China, have changed.
Conclusion
Previous hospitalization, ulcer size >4cm
2
, surgical therapy and CRP were independent risk factors for MDROs infection in diabetic foot patients. Identifying these risk factors can help us identify the high-risk patients of diabetic foot with MDRO infection early. More attention to high-risk patients and more aggressive isolation precautions may reduce the incidence of MDRO infection in diabetic foot patients.
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