Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics. It has been challenging to assess mRNA packaging characteristics in LNPs, including payload distribution and capacity, which are critical to understanding structure-property-function relationships for further carrier development. Here, we report a method based on the multi-laser cylindrical illumination confocal spectroscopy (CICS) technique to examine mRNA and lipid contents in LNP formulations at the single-nanoparticle level. By differentiating unencapsulated mRNAs, empty LNPs and mRNA-loaded LNPs via coincidence analysis of fluorescent tags on different LNP components, and quantitatively resolving single-mRNA fluorescence, we reveal that a commonly referenced benchmark formulation using DLin-MC3 as the ionizable lipid contains mostly 2 mRNAs per loaded LNP with a presence of 40%–80% empty LNPs depending on the assembly conditions. Systematic analysis of different formulations with control variables reveals a kinetically controlled assembly mechanism that governs the payload distribution and capacity in LNPs. These results form the foundation for a holistic understanding of the molecular assembly of mRNA LNPs.

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Patients who sustain peripheral nerve injuries (PNIs) are often left with debilitating sensory and motor loss. Presently, there is a lack of clinically available therapeutics that can be given as an adjunct to surgical repair to enhance the regenerative process. Insulin-like growth factor-1 (IGF-1) represents a promising therapeutic target to meet this need, given its well-described trophic and anti-apoptotic effects on neurons, Schwann cells (SCs), and myocytes. Here, we review the literature regarding the therapeutic potential of IGF-1 in PNI. We appraised the literature for the various approaches of IGF-1 administration with the aim of identifying which are the most promising in offering a pathway toward clinical application. We also sought to determine the optimal reported dosage ranges for the various delivery approaches that have been investigated.

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Both endoscopic and open carpal tunnel release (E-and OCTR) are well-tolerated operations. Endoscopic carpal tunnel release is associated with lower immediate postoperative pain scores compared with open carpal tunnel release 1 ; however, studies on postoperative opioid requirements and need for therapy have been limited. Due to the high volume performed, differences in outcomes associated with each technique may have significant implications for society and the healthcare system. The aim of our study was to compare endoscopic and open approaches to CTR in terms of postoperative opioid refills and occupational therapy requirements.

by their duration of effect, necessitating frequent redosing. We aim to develop a nanoparticle-based delivery system to extend BoNT release and characterize its release profile. METHODS:Botulinum toxin A (BoNTa) neuromodulators were encapsulated within polymeric nanoparticles (NPs) using a kinetically controlled microfluidic assembly method. Dynamic light scattering was used to measure particle size and uniformity. ELISA was used to quantify the protein release profile. RESULTS:Particle sizes were uniform with most particles centered at 100nm and nearly all particles between 50-200nm. A tunable release profile was achieved, in which BoNTa could be released linearly or with an initial bolus followed by sustained release at the desired rate. Reproducibility of NP performance was demonstrated in 3 independent trials. Our early in-vivo and mechanistic studies have demonstrated preservation of toxin bioactivity and extended therapeutic effect in a rat model. CONCLUSIONS:We developed a novel nanoparticle-based Botox formulation capable of providing long-acting release of neuromodulator with tunable kinetics at designated dosage. This sustained release delivery modality enables superior therapeutic outcomes with less frequent re-dosing.

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p=0.045), HER-2 (n=10, mean difference 0.154, p=0.031), and BRCA1 (n=9, mean difference 0.225, p=0.015). There was no difference in post-implant (one-month and sixmonth) antibody responses to tetanus, CEA, MMP11, and HER-3. Confirmatory studies show elevated presence of B cells in peri-implant breast tissue compared to implant naïve breast tissue.CONCLUSION: Women with cosmetic breast implants have elevated antibody responses to common breast cancer proteins as early as one month post implant placement, and sustained at six months. Further studies will elucidate the immunologic mechanism for this potential cancer surveillance role.