The microstructures of doxorubicin-loaded micelles prepared from block polymers His(x)Lys10 (x = 0, 5, 10) conjugated with docosahexaenoic acid (DHA) are investigated under different pH conditions, using dissipative particle dynamics (DPD) simulations. The conformation of micelles and the DOX distributions in micelles were obviously influenced by pH values and the length of the histidine segment. At pH >6.0, the micelles self-assembled from the polymers were dense and compact. The drugs were entrapped well within the micellar core. The particle size increases as the histidine length increases. With the decrease of pH value to be lower than 6.0, there was no distinct difference for the micelles self-assembled from the polymer without histidine residues. However, the micelles prepared from the polymers with histidine residues shows a structural transformation from dense to swollen conformation, leading to an increased particle size from 10.3 to 14.5 DPD units for DHD-His10Lys10 micelles. This structural transformation of micelles can accelerate the DOX release from micelles under lower pH conditions. The in vitro drug release from micelles is accelerated by the decrease of pH value from 7.4 (physiological environment) to 5.0 (lysosomal environment). The integration of simulation and experiments might be a valuable method for the optimization and design of biomaterials for drug delivery with desired properties.
The focus of solid microneedles technology to date has
largely
been on cosmetology, vaccination, and insulin delivery, etc. However,
limited information is available about the safety of solid polymer
microneedles applied in different parts of the human body. In consideration
of the different application sites of cosmetology, vaccination, and
insulin delivery involved with microneedles technique, factors influencing
user acceptance to microneedles including the length and density as
well as the size of microneedle patches were systematically investigated
by applying different microneedle patches on the forehead, forearm,
and abdomen skins of 18 healthy human participants. Multiple insertion
tests demonstrated that solid microneedles with a length of 400 μm,
a density of 100 MN/cm2, and an array size of 10 ×
10 were optimal for forehead pretreatment. Microneedles with lengths
of 400 and 600 μm, densities of 49 and 100 MN/cm2, and an array size of 10 × 10 caused less pain and slight skin
irritation in the forearm, whereas 400 μm height, 49 and 100
MNs/cm2 densities, and 5 × 5, 10 × 10, and 10
× 20 arrays of the solid microneedles were not considered painful
and were well-tolerated in abdomen insertion. In conclusion, the optimization
of the dimensions of microneedles according to application sites could
improve medication compliance and the safety of clinical use of solid
microneedles.
BackgroundPrevious studies have confirmed the predicted value of serum glycated albumin (GA) in atherosclerotic cardiovascular disease. However, the relationship between GA and the development of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation has not been verified in patients with acute coronary syndrome (ACS).Materials and methodsIn this study, 797 patients diagnosed with ACS who underwent re-coronary angiography more than 6 months after the first successful DES-based percutaneous coronary intervention (PCI) were eventually included. Patients were categorized into two groups based on the median GA levels of 14.94%. Moreover, multivariate logistic regression analysis models and the net reclassification improvement and integrated differentiation improvement risk models were constructed to assess the relationship between the GA and DES-ISR in patients with ACS.ResultsThe GA was significantly associated with an increased risk of DES-ISR, upon adjusting for confounding factors (as nominal variate: OR 1.868, 95% CI 1.191–2.932, P = 0.007; as continuous variate: OR 1.109, 95% CI 1.040–1.183, P = 0.002). The addition of GA to a baseline risk model had an incremental effect on the predictive value for DES-ISR (AUC: GA vs. baseline model, 0.714 vs. 0.692, comparison P = 0.017; category-free net reclassification improvement (NRI) 0.080, P = 0.035; integrated discrimination improvement (IDI) 0.023, P < 0.001).ConclusionGA level was significantly associated with a high risk of DES-ISR in patients with ACS treated with PCI. Moreover, the addition of the GA to a baseline risk model has an incremental effect on the predictive potential for DES-ISR.
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