Controlled-release Administration Research Articles

Novel Vectors and Administrations for mRNA Delivery.

mRNA therapy has shown great potential in infectious disease vaccines, cancer immunotherapy, protein replacement therapy, gene editing, and other fields due to its central role in all life processes. However, mRNA is challenging to pass through the cell membrane due to its significant negative charges and degradation from RNase, so the key to mRNA therapy is efficient packaging and delivery of it with appropriate vectors. Presently researchers have developed various vectors such as viruses and liposomes, but these conventional vectors are now difficult to meet the growing requirement like safety, efficiency, and targeting, so many novel delivery vectors with unique advantages have emerged recently. This review mainly introduces two categories of novel vectors: biomacromolecules and inorganic nanoparticles, as well as two novel methods of control and administration based on these novel vectors: controlled-release administration and non-invasive administration. These novel delivery strategies have the advantages of high safety, biocompatibility, versatility, intelligence, and targeting. This paper analyzes the challenges faced by the field of mRNA delivery in depth, and discusses how to use the characteristics of novel vectors and administrations to solve these problems.

Biocompatible oligo-oxazoline crosslinkers: Towards advanced chitosans for controlled dug release

Chitosan, a natural and abundant biopolymer has been long explored as a biocompatible material for the preparation of drug delivery devices. This strategy has been mostly accomplished using chemically crosslinked chitosan leading to more stable scaffolds. However, crosslinking has been shown to reduce both biocompatibility and swelling. In this work chitosan was crosslinked with novel biocompatible crosslinkers, based on oligo-oxazolines and glycidyl methacrylate copolymers, leading to patches with a very high swelling capacity. Dexamethasone therapeutics is strongly enhanced by a controlled release administration. This study shows that oligo-oxazoline-crosslinked chitosan is a suitable biomaterial for loading and controlled release of dexamethasone.

Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy

The complexity of pain from laparoscopic cholecystectomy and the need for treating incident pain provide rationale for multipharmacological analgesia. We investigated the preoperative administration of controlled-release (CR) oxycodone as transition opioid from remifentanil infusion for pain after laparoscopic cholecystectomy. Fifty consecutive patients undergoing laparoscopic cholecystectomy were randomly, double-blindly assigned to treatment group (n=25, CR oxycodone: 1 h before surgery and 12 h after the first administration) or to the control group (n=25, placebo: administered at the same intervals). General anaesthesia was maintained with propofol and remifentanil target-controlled infusions (TCIs). All patients received ketorolac 30 mg i.v. Tramadol i.v. was administered for patient-controlled analgesia (PCA) postoperatively. Numerical rating scale for pain at rest and at movement (NRSr and NRSi), tramadol consumption, times to readiness to surgery and awakening, times to modified Aldrete's and modified Post-Anesthetic Discharge Scoring System (PADSS)>9 and side effects were evaluated. All NRSr and NRSi and tramadol consumption were significantly lower in the treatment group. The oxycodone group showed higher modified Aldrete's scores at each time and reached a PADSS>9 faster. Side effects and postoperative nausea and vomiting episodes were comparable. We demonstrated the success of a multipharmacological treatment including opioid premedication with CR oxycodone used as transition opioid for TCI remifentanil infusion; the treatment group showed lower pain scores and rescue analgesic consumption, shorter time to discharge from recovery room and from surgical ward, and the same incidence of side effects, comparably to controls.