ABSTRACT
Introduction: In the context of the current opioid crisis, non-pharmacologic approaches to pain management have been considered important alternatives to the use of opioids or analgesics. Advancements in nano and quantum technology have led to the development of several nanotransporters, including nanoparticles, micelles, quantum dots, liposomes, nanofibers, and nano-scaffolds. These modes of nanotransporters have led to the development of new drug formulations. In pain medicine, new liposome formulations led to the development of DepoFoam™ introduced by Pacira Pharmaceutical, Inc. (Parsippany, NJ, USA). This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine. In 2021, Heron Therapeutics (San Diego, CA, USA) created Zynrelef™, a mixture of bupivacaine and meloxicam. Advancements in nanotechnology have led to the development of devices/patches containing millions of nanocapacitors. Data suggest that these nanotechnology-based devices/patches reduce acute and chronic pain. Methods: Google and PubMed searches were conducted to identify studies, case reports, and reviews of medical nanotechnology applications with a special focus on acute and chronic pain. This search was based on the use of keywords like nanotechnology, nano and quantum technology, nanoparticles, micelles, quantum dots, liposomes, nanofibers, nano-scaffolds, acute and chronic pain, and analgesics. This review focuses on the role of nanotechnology in acute and chronic pain. Results: (1) Nanotechnology-based transporters. DepoDur™, administered epidurally in 15, 20, or 25 mg single doses, has been demonstrated to produce significant analgesia lasting up to 48 h. Exparel™ is infiltrated at the surgical site at the recommended dose of 106 mg for bunionectomy, 266 mg for hemorrhoidectomy, 133 mg for shoulder surgery, and 266 mg for total knee arthroplasty (TKA). Exparel™ is also approved for peripheral nerve blocks, including interscalene, sciatic at the popliteal fossa, and adductor canal blocks. The injection of Exparel™ is usually preceded by an injection of plain bupivacaine to initiate analgesia before bupivacaine is released in enough quantity from the depofoarm to be pharmacodynamically effective. Finally, Zynrelef™ is applied at the surgical site during closure. It was initially approved for open inguinal hernia, abdominal surgery requiring a small-to-medium incision, foot surgery, and TKA. (2) Nanotechnology-based devices/patches. Two studies support the use of nanocapacitor-based devices/patches for the management of acute and chronic pain. A randomized study conducted on patients undergoing unilateral primary total knee (TKA) and total hip arthroplasty (THA) provided insight into the potential value of nanocapacitor-based technology for the control of postoperative acute pain. The results were based on 2 studies, one observational and one randomized. The observational study was conducted in 128 patients experiencing chronic pain for at least one year. This study suggested that compared to baseline, the application of a nanocapacitor-based Kailo™ pain relief patch on the pain site for 30 days led to a time-dependent decrease in pain and analgesic use and an increase in well-being. The randomized study compared the effects of standard of care treatment to those of the same standard of care approach plus the use of two nanocapacitor-based device/patches (NeuroCuple™ device) placed in the recovery room and kept in place for three days. The study demonstrated that the use of the two NeuroCuple™ devices was associated with a 41% reduction in pain at rest and a 52% decrease in the number of opioid refills requested by patients over the first 30 days after discharge from the hospital. Discussion: For the management of pain, the use of nano-based technology has led to the development of nano transporters, especially focus on the use of liposome and nanocapacitors. The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation. In these cases, the technology is used to prolong the duration of action of drugs included in the preparation. Another indication of nanotechnology is the development of nanocapacitor device or patches. Although, data obtained with the use of nanocapacitors are still limited, evidence suggests that the use of nanocapacitors devices/patches may be interesting for the treatment of both acute and chronic pain, since the studies conducted with the NeuroCuple™ device and the based Kailo™ pain relief patch were not placebo-controlled, it is clear that additional placebo studies are required to confirm these preliminary results. Therefore, the development of a placebo devices/patches is necessary. Conclusions: Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches.
ABSTRACT
Purpose: The FDA recently approved Zynrelef® (A viscous solution of extended release of bupivacaine and meloxicam) to be applied at closure and providing postoperative analgesia for 72 hrs. Although the FDA didn't restrict the use of nerve blocks in combination with this formulation, the safety and efficacy of such a combination has yet to be documented. This quality improvement study investigated this combination within the FDA-approved indications. Methods: Selected surgeons at two hospitals were chosen to use Zynrelef®. According to the standard of care, surgeons were also allowed to request single nerve blocks before surgery. The type of nerve blocks (unilateral or bilateral) performed included quadratus lumborum and paravertebral blocks for abdominal surgery, and adductor canal block for total knee replacement. Each block was performed with 20 mL of 0.375% bupivacaine (n=129) or 0.5% of ropivacaine (n=30). Pain scores, opioid consumption, and prescription refill requests at discharge were recorded. Patients discharged on the same day of surgery were separated into two groups-those who received single nerve blocks plus an Zynrelef® (group 1) vs. those receiving Zynrelef® only (group 2) and was analyzed using an un-paired t-test. Results: A total of 184 patients received Zynrelef®, including 25 patients who didn't receive blocks, 44 who received unilateral blocks and 114 who received bilateral blocks. No symptoms suggestive of Local Anesthetic Toxicity (LAST) were observed. The use of the combination was associated with a 50% reduction in the number of patients filling their opioid prescription. Conclusion: This study provides evidence that the combination of a single unilateral or bilateral nerve block with Zynrelef® is safe.
ABSTRACT
Introduction COVID-19 and influenza are primarily respiratory diseases, have similar symptoms with most patients developing mild to moderate illness, and show similar features on chest X-rays. We hypothesize that patients seeking treatments at the emergency department (ED) due to COVID-19 or influenza infection will have similar severity levels of features on chest X-rays, with most of them demonstrating normal to mildly abnormal chest X-ray findings. Methods Chest X-ray images of 312 COVID-19 patients and 312 influenza patients were obtained from the teaching files of a general diagnostic radiologist. Images from each of these two groups were reviewed and classified. Based on the severity levels of lung abnormalities, each image was categorized into one of four categories: normal, mildly abnormal, moderately abnormal, or severely abnormal. The total number of images in each category within each disease group was counted, and the percentage was calculated compared to the total number of images analyzed in that group. Results from both groups were then compared. Results The severity levels of chest X-ray abnormalities were similar between the COVID-19 group and the COVID-negative influenza group at the time of ED visits, with most images being normal or mildly abnormal. The percentages of the images categorized as normal, mildly abnormal, moderately abnormal, and severely abnormal in the COVID-19 group and the influenza group were 38-39%, 28-29%, 22-21%, and 12-11%, respectively. Conclusion Our findings suggest that in the ED setting, no distinction can be made between COVID-19 and Influenza infections if based just on chest X-rays.
ABSTRACT
Hypothesis: Magnetic nanoparticles (MNPs) for cochlear drug delivery can be precisely engineered for biocompatibility in the cochlea. Background: MNPs are promising drug delivery vehicles that can enhance the penetration of both small and macromolecular therapeutics into the cochlea. However, concerns exist regarding the application of oxidative, metal-based nanomaterials to delicate sensory tissues of the inner ear. Translational development of MNPs for cochlear drug deliver requires specifically tuned nanoparticles that are not cytotoxic to inner ear tissues. We describe the synthesis and characterization of precisely tuned MNP vehicles, and their in vitro biocompatibility in murine organ of Corti organotypic cultures. Methods: MNPs were synthesized via 2-phase ligand transfer process with precise control of nanoparticle size. Core and hydrodynamic sizes of nanoparticles were characterized using electron microscopy and dynamic light scattering, respectively. In vitro biocompatibility was assayed via mouse organ of Corti organotypic cultures with and without an external magnetic field gradient. Imaging was performed using immunohistochemical labeling and confocal microscopy. Outer hair cell, inner hair cell, and spiral ganglion neurites were individually quantified. Results: Monocore PEG-MNPs of 45 and 148 nm (mean hydrodynamic diameter) were synthesized. Organ of Corti cultures demonstrated preserved outer hair cell, inner hair cell, and neurite counts across 2 MNP sizes and doses, and irrespective of external magnetic field gradient. Conclusion: MNPs can be custom-synthesized with precise coating, size, and charge properties specific for cochlear drug delivery while also demonstrating biocompatibility in vitro.
