Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is increasingly used for a diverse range of wounds. Meanwhile, the topical wound irrigation solution consisting of polyhexamethylene biguanide and betaine (PHMB-B) has shown efficacy in managing wound infections. However, the effectiveness of this solution as a topical instillation solution for NPWTi-d in patients with diabetic foot infections (DFIs) has not been thoroughly studied. The objective of this retrospective study was to evaluate the impact of using PHMB-B as the instillation solution during NPWTi-d on reducing bioburden and improving clinical outcomes in patients with DFIs. Between January 2017 and December 2022, a series of patients with DFIs received treatment with NPWTi-d, using either PHMB-B or normal saline as the instillation solution. Data collected retrospectively included demographic information, baseline wound characteristics, and treatment outcomes. The study included 61 patients in the PHMB-B group and 73 patients in the normal saline group, all diagnosed with DFIs. In comparison to patients treated with normal saline, patients with PHMB-B exhibited no significant differences in terms of wound bed preparation time (P = 0.5034), length of hospital stay (P = 0.6783), NPWTi-d application times (P = 0.1458), duration of systematic antimicrobial administration (P = 0.3567), or overall cost of hospitalization (P = 0.6713). The findings of the study suggest that the use of either PHMB-B or normal saline as an instillation solution in NPWTi-d for DFIs shows promise and effectiveness, yet no clinical distinction was observed between the two solutions.

OBJECTIVE: To assess the use of non-insulin antidiabetic medicines in China.
METHODS: We analysed the national procurement data for 29 non-insulin antidiabetic medicines from nine subgroups in China from 2015 to 2022. We estimated the number of defined daily doses (DDDs) procured per year in seven regions of China for nine subgroups and adjusted the data by the number of patients with diabetes. For each subgroup, the regional ratio was calculated by comparing the procurement per patient in each region with the procurement nationwide. The regional disparity was the difference between the highest and lowest regional ratios. We compared the medication patterns across regions.
RESULTS: Nationally, between 2015 and 2022, the number of DDDs per patient increased from 14.45 to 47.37. The two most commonly used categories were sulphonylurea and biguanides, which increased from 7.04 to 15.39 (119%) and 3.28 to 11.11 (239%) DDDs per patient, respectively. The procurement of new drugs (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists) increased quickly and had >5000% relative changes. Particularly for sodium-glucose cotransporter type 2 inhibitors, it increased from 0.08 to 5.03 DDDs (6662%). The southwest region had the highest relative change (319%), while the southern region had the lowest (118%). Biguanide and thiazolidinediones had the lowest (1.19) and highest level (2.21) of regional disparity in 2022, respectively.
CONCLUSIONS: The procurement of non-insulin antidiabetic medicines in China has increased a lot from 2015 to 2022. In terms of DDDs per patient, sulphonylurea ranked first, followed by metformin. The procurement of new drugs increased greatly. A large regional disparity existed in medicine usage and patterns.

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs-PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-β1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs-PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-β1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs-PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.

Facemasks play a significant role as personal protective equipment during the COVID-19 pandemic, but their longevity is limited by the easy dissipation of electrostatic charge and the accumulation of bacteria. In this study, nanofibrous membranes composed of polyacrylonitrile and chitosan biguanide hydrochloride (PAN@CGH) with remarkable antibacterial characteristics were prepared through the coaxial electrospinning process. Particulate matter could be efficiently captured by the fibrous membrane, up to 98 % or more, via polarity-dominated forces derived from cyano and amino groups. As compared commercial N95 masks, the PAN@CGH was more resistant to a wider variety of disinfection protocols. Additionally, the nanofibrous membrane could kill >99.99 % of both Escherichia coli and Staphylococcus aureus. Based on these characteristics, PAN@CGH nanofibrous membrane was applied to facial mask, which possessed an excellent and long-lasting effect on the capture of airborne particles. This work may be one of the most promising strategies on designing high-performance face masks for public health protection.

In clinical chemotherapy, albumin-bound paclitaxel (Abraxane) can improve the tumor targeting property and therapeutic efficacy of paclitaxel (PTX) against orthotopic malignancies. However, patients with metastatic cancer have a poor prognosis, probably due to the instability, chemoresistance, and inability of albumin-bound paclitaxel to alter the tumor microenvironment. Here we propose a new biguanide-modified albumin-based nanoplatform that encapsulates paclitaxel for the effective treatment of metastatic cancer. The PTX is encapsulated in poly (lactic-co-glycolic acid) cores coated with biguanide-modified albumin (HSA-NH). The functionalized nanoparticles (HSA-NH NPs) exhibit a remarkable stable profile with low drug release (P < 0.05 versus Abraxane), target tumor tissues, suppress epithelial-mesenchymal transition (EMT) events for anti-metastatic effects, and reduce the phenotype of cancer stem cells. As a result, HSA-NH NPs effectively prolong animal survival (55 days) by inhibiting not only primary tumor growth but also metastasis. This study provides proof of concept that the biguanide-anchored albumin-based nanoplatform encapsulating PTX is a powerful, safe, and clinically translational strategy for the treatment of metastatic cancer. STATEMENT OF SIGNIFICANCE: Albumin-bound paclitaxel (Abraxane) can increase paclitaxel\'s tumor targeting and therapeutic efficacy in clinical cancer treatments such as breast cancer. However, the instability, chemoresistance, and lack of tumor microenvironment modulation of albumin-bound paclitaxel may lead to poor therapeutic efficacy in metastatic cancer patients. Here we develop biguanide-anchored albumin-based nanoplatforms that encapsulate paclitaxel (HSA-NH NPs) for metastatic cancer treatment. Poly(lactic-co-glycolic acid) (PLGA) cores encapsulating paclitaxel improve the stability of HSA-NH NPs. Based on the activities of metformin, biguanide-anchored albumin adsorbed on PLGA cores improves paclitaxel efficacy, inhibits various aberrant changes during epithelial-mesenchymal transition, and reduces tumor cell stemness. The biguanide-anchored albumin-based nanoplatform encapsulating PTX can serve as a potent, safe, and clinically translational approach for metastatic cancer therapies.

Raw halloysite was purified by using sodium hexametaphosphate and utilized as the solid-phase extraction sorbent for the determination of biguanides from dietary supplements. The purified halloysite was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The purified halloysite interacted with biguanides through hydrophilic interaction and ion exchange on account of its abundant hydroxyl groups and negative charge. Compared with traditional extraction methods based on hydrophobic interaction and/or ion exchange, the purified halloysite adsorbed more biguanides due to hydrophilicity and ion exchange, with a sample loading volume of up to 100 mL at least. Excellent reproducibility of halloysite purification was achieved, with within-batch (n = 3) and batch-to-batch (n = 3) relative standard deviations in the ranges of 1.5-4.2% and 5.6-8.8%, respectively. Coupled with reversed-phase liquid chromatography-tandem mass spectrometry, a low limit of detection of 0.3 μg kg-1 was obtained. The intra- and inter-day mean recoveries of the biguanides spiked at three levels in dietary supplements were within the ranges of 88.5-107.2% and 86.4-102.0%, respectively. The intra- and inter-day precisions were within the ranges of 1.5-6.4% and 5.4-9.9%, respectively. These results indicated that the developed method is efficient for the determination of trace biguanides in dietary supplements.

Commercially available, strongly basic anion-exchange resins with quaternary ammonium groups have been widely used in the purification of natural plant extracts. However, under the condition of high temperature (greater than 60 °C), these resins could not be used for long periods because of the Hofmann degradation of the strongly basic groups. In this work, the synthesis of novel, thermally stable, strongly basic resins, which has a cross-link biguanide structure, was reported. The mechanism of thermal degradation was investigated, and the result indicated that not only the stability of the functional group but also the link mode between the functional group and the resin matrix should influence the thermal stability of the resin. In our experiment, the PDG2 resin was selected to separate sodium copper chlorophyllin (SCC), a type of edible pigment derived from plants, due to its optimal thermal stability and adsorption capacity. The adsorption mechanism and thermodynamics of PDG2 were also investigated. The results demonstrated that the main adsorption affinity of PDG2 toward SCC was due to the synergistic effects of the hydrophobic and ionic interactions, and the rise in temperature will benefit the adsorption equilibrium, which differed from the equilibrium for lutein. Therefore, under suitable gradient desorption conditions, a high-purity SCC extract was prepared. After eight cycles, the adsorption capacity of the PDG2 remained constant and reproducible at a high temperature (70 °C).

Biofilm formation on biomedical devices is a major cause of device-associated infection. Traditional antibiotic treatment for biofilm-associated infection increases the risk of multidrug resistance. Thus, there is an urgent need to develop antibiotic-free strategies to prevent biofilm formation on biomedical devices. Herein, we report a layer-by-layer strategy to construct an antifouling and bactericidal dual-functional coating for silicone rubber (SR)-based substrates. Five zwitterionic active ester copolymers, p(SBMA-co-NHSMA), with varied zwitterionic pSBMA components that ranged from 50 to 90% (molar ratio) were precisely prepared. Based on -NH2/NHS chemistry, a zwitterionic pSBMA antifouling coating was successfully constructed on an -NH2-activated SR surface, while a biguanide polymer (PHMB) bactericidal coating was consequently tethered. The relationship between the composition of the polymeric coating and the overall antibacterial property (antifouling and bactericidal) that was endowed to the SR surface was established. The in vitro and in vivo results consistently showed that the optimal p(SBMA-co-NHSMA) copolymer (SBMA/NHSMA with molar percentage of 70/30) synergistically utilized antifouling and bactericidal abilities to endow a highly efficient overall antibacterial property (near 100% antibacterial ratios) to SR70-PHMB substrates without compromising cellular viability. This strategy may be applied to the many SR-based biomedical implants and devices where an antibacterial surface is required.

At present, the tumor\'s poor oxygen perfusion and limited tumor drug permeation are the major bottlenecks that limit the therapeutic effectiveness of the oxygen-sensitive antitumor therapies, like doxorubicin (Dox)-mediated chemotherapy and photodynamic therapy (PDT). To our best knowledge, the abnormal tumor mitochondria oxidative phosphorylation (OXPHOS) was the vital cause of such phenomenon, which induced the hypoxia tumor microenvironment and enhanced drug efflux from tumor cells via enhanced multidrug resistance protein 1 (MDR-1) expression. In this study, it was newly revealed that biguanide-modified chitosan (Bi-Ch) possessed ideal mitochondria depression capacity, leading to the following decreased dosage needed to disrupt mitochondrial function to reverse tumor hypoxia and depress MDR-1 expression. By doing this, Bi-Ch effectively enhanced Dox accumulation in tumor cells and amplified its cytotoxicity owing to the amplified ROS generation by Dox. Therefore, Bi-Ch could be used to improve the efficacy of oxygen-sensitive tumor therapies in vitro.

UNASSIGNED: Diabetes mellitus (DM) is associated with immune dysregulation, while sulfonylureas or biguanides have been linked to anti-inflammatory mechanisms. In this study, we aimed to examine the occurrence rate of rheumatoid arthritis (RA) among DM patients and its incidence rate between different treatments.
UNASSIGNED: This cohort study used the Taiwan National Health Insurance Research Database between 1997 and 2013 to evaluate the primary outcomes of the preventive role of sulfonylureas or biguanides in the development of RA. We used the Chi-square test for categorical variables and Cox proportional hazard regression and log-rank test to explore the time for development of RA in DM patients. Logistic regression was adopted to estimate the odds ratio of RA in different dosages of medication exposure.
UNASSIGNED: Our cohort study included 94,141 DM cases. The risk of RA development of non-sulfonylureas/biguanides users among the DM group in each analysis was set as the reference, and the adjusted hazard ratio of RA in DM patients who were using sulfonylureas or biguanides was 0.73 (95% confidence interval 0.60-0.90). Within 1 year before the index date, compared with no-biguanides users, patients with more than 180 days of prescription of biguanides had a significantly lower RA risk. Similarly, the significantly lower risk of RA was still observed in DM patients who had more than 365 days of prescription of sulfonylurea within 2 or 3 years before the index date of first RA visit (all p < 0.05).
UNASSIGNED: Our data suggest that sulfonylureas or biguanides are associated with a lower rate of RA development in patients with DM; the effect of biguanides appeared more rapid than that of sulfonylureas, but the sulfonylureas might have a longer effect on lowering RA development incidence.