ABSTRACT
Messenger RNA(mRNA)medicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.
ABSTRACT
Background/Aims The Fracture Liaison Service (FLS) identifies patients >50 who have sustained a fragility fracture (FF). These patients need prompt assessment and decision on appropriate treatment for osteoporosis in order to reduce their risk of sustaining further FFs. Without treatment, 1/5 patients can go on to have a further FFs which carry significant risk to mortality and morbidity. Zoledronate is a bone agent that halves the risk of another FF. Patients with a neck of femur fracture (#NOF) present as one of the most at-risk groups for a further FF. These patients are generally elderly and frail and attendance to outpatient hospital appointments are difficult. Therefore, transforming the FLS from an out-patient-based service, to one that is streamlined to systematically identify and opportunistically treat patients whilst they are still in hospital means delivering timely, effective and efficient patient-centred care. Methods We used various Plan-Do-Study-Act cycles to aim to deliver Zoledronate to>=90% of appropriately assessed in-patients >60 who have had a #NOF within a year of commencing QIP. Results PDSA cycle 1-Involvement of ortho-geriatrician: P-Improve working relationship with ortho-geriatrician with an interest in bone health over a 6-month period;D-Regular meetings with wider MDT;S-Priority of bone health assessments made greater through ward round documentation;A-Expand knowledge throughout the wider ortho-geriatrician team. PDSA cycle 2-Timing of Zoledronate delivery: P-Literature review regarding delivery of Zoledronate timing;D-Discuss as MDT;SNo evidence to suggest delay in fracture healing if given on day 7;AAdopted process and communicated. PDSA cycle 3-FLS team on the wards as a result of PDSA cycle 2 not improving treatment outcomes: P-FLS nurses to join ortho-geriatrician ward round twice-weekly for 3- month trial period;D-Bank holidays and spike in Covid cases presented a challenge. Solution: Improvement of MDT relationships;S-At the end of the trial period an increase in patients who received treatment was shown and proved our prediction;A-Adaptation to documentation in FLS to streamline and reduce duplication. Conclusion The ability to deliver Zoledronate to>=90% of appropriate patients with a #NOF as an inpatient was reached after 8 months of initiating QIP. Furthermore, maintaining this was consistently achieved throughout the following year and beyond. A few of the main reasons for this included earlier drug delivery, having a dedicated ortho-geriatrician as part of the FLS, and the FLS team attending the wards. A prompt bone health assessment of patients has enabled appropriate treatment to be delivered efficiently. The delivery of Zoledronate as an in-patient has meant that a significantly greater proportion of patients receive treatment, and sooner, in comparison to awaiting an outpatient assessment (that they may not attend). Therefore, this QIP has demonstrated time- and cost-effective management of patients with #NOF requiring Zoledronate.
ABSTRACT
Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.