pH-Responsive Nanoparticles for Drug and Gene Delivery

Stimuli-sensitive polymers that respond to temperature, pH, light, ionic strength, and electric or magnetic fields are attractive for use in drug delivery, diagnostics, and sensing. Much attention has been paid to the use of pH-sensitive polymers for oral drug delivery, gene delivery, and insulin delivery, where a physiological pH shift facilitates swelling. In this research, pH-sensitive poly N,N-dimethylaminoethyl methacrylate (DMAEMA) / 2-hydroxyethyl methacrylate (HEMA) nanoparticles were prepared for the triggered release of paclitaxel within a tumor microenvironment. Monodispersed nanoparticles were synthesized by forming an O/W emulsion followed by photopolymerization. Particles were characterized by transmission electron microscopy, dynamic light scattering, electrophoresis, and cytotoxicity. High release rates and swelling ratios are achieved at low pH, low crosslinking density, and high content of DMAEMA. Cell viability studies indicate that pH-sensitive DMAEMA/HEMA nanoparticles are not cytotoxic and may be used as an efficient, feedback-regulated drug delivery carrier. DMAEMA/HEMA nanoparticles were also used as gene carriers with nearly 100% encapsulation rate due to their ability to swell at low pH which may overcome the obstacles of endosomal release and low transfection efficiency of nonviral gene delivery vectors. Once internalized via the endocytosis pathway, the nanoparticles undergo osmotic swelling facilitating endosomal escape of DNA to the cytoplasm. For intracellular tracking, particles were conjugated with quantum dots and examined by confocal microscopy at different time points. To examine the efficacy of DMAEMA/HEMA nanoparticles in facilitating endosomal escape of pDNA encoded EGFP, HeLa cells were incubated with DNA-loaded nanoparticles for 24 and 48 h. Enhanced gene transfection and particle uptake were achieved by modulating matrix elasticity and pH sensitivity. After a 48 h incubation, the transfection efficiency obtained by using DNA-loaded DMAEMA/HEMA nanoparticles was 45 ± 4.8%, in comparison to 40 ± 3.1% for PEI/DNA complexes. Our results show that elastic and pH-sensitive DMAEMA/HEMA nanoparticles enable higher gene expression at 24 and 48 h than polyethyleneimine (PEI)/DNA and poly-L-lysine (PLL)/DNA complexes without the drawback of cytotoxicity

Bioresponsive matrices in drug delivery

For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli

Bioresponsive matrices in drug delivery

For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.Engineering and Applied Science

Self-Isolated Dual-Mode High-Pass Birdcage RF Coil for Proton and Sodium MR Imaging at 7 T MRI

This study presents the feasibility of a dual-mode high-pass birdcage RF coil to acquire MR images at both 1H and 23Na frequencies at ultra-high-field MR scanner, 7 T. A dual-mode circuit (DMC) in the dual-mode birdcage (DMBC) RF coil operates at two frequencies, addressing the limitations of sensitivity reduction and isolation between two frequencies as in traditional dual-tuned RF coil. Finite-difference time-domain (FDTD) based electromagnetic (EM) simulations were performed to verify the RF coil at each frequency on the three-dimensional human head model. The DMBC RF coil resonated at proton (1H) and sodium (23Na) frequencies, and also single-tuned high-pass birdcage RF coils were constructed for both 1H and 23Na frequencies. The bench test performance of the RF coils was evaluated using network analysis parameters, including the measurement of scattering parameters (S-parameters) and quality factors (Q-factors). Q-factor of the DMBC coil at 1H port was 10.2% lower than that of 1H single-tuned birdcage (STBC) coil, with a modest SNR reduction of 6.5%. Similarly, the Q-factor for the DMBC coil at 23Na port was 12.3% less than that of 23Na STBC coil, and the SNR showed a minimal reduction of 5.4%. Utilizing the DMBC coil, promising 1H and 23Na MR images were acquired compared to those by using STBC coils. In conclusion, deploying a DMBC 1H/23Na coil has been demonstrated to overcome traditional constraints associated with dual-tuned RF coils, achieving this with only nominal signal attenuation across both nuclei operational frequencies

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus

Burnout and peritraumatic distress of healthcare workers in the COVID-19 pandemic

Background To evaluate the current status of emotional exhaustion and peritraumatic distress of healthcare workers (HCWs) in the COVID-19 pandemic, and identify factors associated with their mental health status. Methods An online survey involving 1068 of consented HCWs that included nurses, physicians, and public health officers was conducted in May 2020. Descriptive statistics and multivariate regression analyses were performed on the collected data. Results Although no significant difference in peritraumatic distress was observed among the surveyed HCWs, the workers’ experience of emotional exhaustion varied according to work characteristics. Respondents who were female, older, living with a spouse, and/or full-time workers reported higher levels of emotional exhaustion. Public health officers and other medical personnel who did not have direct contact with confirmed patients and full-time workers had a higher level of peritraumatic distress. Forced involvement in work related to COVID-19, worry about stigma, worry about becoming infected, and perceived sufficiency of organizational support negatively predict emotional exhaustion and peritraumatic distress. Conclusions Job-related and emotional stress of HCWs should not be neglected. Evidence-based interventions and supports are required to protect HCWs from mental illness and to promote mental health of those involved in the response to the COVID-19 pandemic.This work was supported by the Gyeonggi-do Public Health Policy Institute, funded by the Gyeonggi-do Province Government, South Korea. The funding body had roles in the design of the study, data collection and analysis