Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose

Sharifi, Farrokh; Meqbil, Yazan J; Otte, Andrew; Gutridge, Anna; Blaine, Arryn T.; Rijn, Richard M. van; Park, Kinam

doi:10.1007/s11095-021-03069-x

Cited by 3 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Formulation or processing parameters and respective mechanistic effect on the microparticles coupled with their expected performance impact. Drug release rate decreases [43][44][45][46][47] PLGA molecular weight (MW) increase Low MW polymer more soluble in an organic phase → • Slow solidification resulting in porous microparticles • Degradation rate decrease Drug release rate decreases [48][49][50] Drug loading increase Increase of drug:PLGA ratio Drug release rate increases [ 10,51,52] Polymer concentration increase • Increase in viscosity delays drug diffusion from droplets • Polymer precipitates faster on surface Encapsulation efficiency increases [ 53,54] Emulsifier concentration increase Decrease in particle size Drug release rate increases [ 55,56] Energy input increase (e.g., homogenization speed, sonication amplitude)…”

Section: Skin Formationmentioning

confidence: 99%

“…PLGA is an amorphous copolymer with tunable degradation rate, flexibility, and firmness. [5] PLGA has been used widely in DOI: 10.1002/adhm.202101427 biomedical and pharmaceutical areas, such as drug delivery, [6][7][8][9][10][11] tissue engineering, and regenerative medicine. [12,13] Characterization of the diffusion, phase separation, gel formation, and quantification of the dynamics of phase inversion began with dark ground imaging techniques.…”

Section: Introductionmentioning

confidence: 99%

“…PLGA is an amorphous copolymer with tunable degradation rate, flexibility, and firmness. [ 5 ] PLGA has been used widely in biomedical and pharmaceutical areas, such as drug delivery, [ 6–11 ] tissue engineering, and regenerative medicine. [ 12,13 ]…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Initial Formation of the Skin Layer of PLGA Microparticles

Sharifi¹,

Otte²,

Park³

2021

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

The Special Issue Dedicated to Professor Nicholas Peppas Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties have been adjusted to control the drug release kinetics and obtain desirable properties of PLGA-based drug delivery systems. The PLGA microparticle formation begins as soon as the drug/PLGA-dissolved in the organic solvent phase (oil phase) is exposed to the water phase. The initial skin (or shell) formation on the oil droplets occurs very quickly, sometimes in the matter of milliseconds, and studying the process has been difficult. The skin formation on the PLGA emulsion droplet surface that can affect the subsequent hardening steps is examined. PLGA droplets with different compositions are prepared. Using collimated light and a high-speed camera made it possible to detect the diffusion of acetonitrile from the oil phase into the water phase during the oil droplet formation. Although the skin formation is not visible on the surface of the oil phase droplet with the current setup, the droplet shapes, solid strand formation, and the difference in the spreading time suggest that the initial contact time between the oil and water phases in the range of a few seconds is critical to the properties of the skin.

show abstract

Section: Skin Formationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Initial Formation of the Skin Layer of PLGA Microparticles

Sharifi¹,

Otte²,

Park³

2021

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hence, we speculated that there might be some drugs that can obviate SIC and PONV effectively and simultaneously. Naloxone, an opioid receptor antagonist, is often adopted to antagonize the residual effects of opioids post-operatively (Dunne, 2018;Sharifi et al, 2021). Recently, low-dose naloxone (roughly defined as 0.05 μg/kg~1 μg/kg) has been reported to mitigate the opioid-induced nausea and vomiting, with unaltered analgesic effect (Barrons and Woods, 2017).…”

Section: Introductionmentioning

confidence: 99%

Low-dose naloxone for prophylaxis of sufentanil-induced choking and postoperative nausea and vomiting

et al. 2022

View full text Add to dashboard Cite

Sufentanil, a potent opioid, serves as the first option for perioperative analgesia owing to its analgesic effect, long duration and stable hemodynamics, whereas its side effects frequently blunt its application. The intravenous (IV) injection of sufentanil during anesthesia induction has high incidence of choking or bucking reaction, which is defined as sufentanil-induced cough (SIC). Moreover, postoperative nausea and vomiting (PONV) is a common and stressful complication, which is also related to the usage of opioid. High incidence of PONV is reported in the patients with SIC. Hence, we sought to determine whether naloxone, an opioid antagonist, at low dose would decrease the incidences of SIC and PONV. 216 female patients undergoing gynecological laparoscopic operation (<2 h) under general anesthesia were recruited in this study, and randomly assigned into two groups: Group N (patients receiving naloxone and Group C (patients receiving vehicle). Sufentanil (0.5 μg/kg within 5 s) was given in anesthesia induction, and low-dose naloxone (1.25 μg/kg) or identical vehicle was initially injected 5 min prior to induction, with the incidence and severity of SIC estimated. Subsequently, naloxone or vehicle was continuously infused at the rate of 0.5 μg/kg/h in the initiation of operation until the end of the operation, and the transverse abdominal fascia block (TAP) was performed for postoperative analgesia. The PONV profiles such as incidence and the severity, grading, and the frequencies of antiemetic usage within 24 h were evaluated, with VAS scores and remedial measures for analgesia during the first 24 h postoperatively were recorded. Our results revealed that one bolus of low-dose naloxone prior to the induction significantly mitigated the incidence of SIC, and intraoperative continuous infusion of low-dose naloxone reduced the incidence and the severity of PONV, so that the postoperative VAS scores and further remedial analgesia were not altered. These results not only provide clinical solutions for prophylaxis of SIC and PONV, but also suggests that opioids may act as a key role in both SIC and PONV, whereas opioid antagonist may hit two tasks with one stone. Moreover, further investigations are required to address the underlying mechanism of SIC and PONV.Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2200064865].

show abstract

The efficacy of nalmefene on anesthetic recovery of patients: a study protocol for a multicenter randomized controlled trial

Liu

Tang

et al. 2023

Trials

View full text Add to dashboard Cite

Introduction So far, the recovery quality after general anesthesia is still unsatisfied. Nalmefene is a drug to treat opioid overdose and reverse opioid actions. We aim to investigate the efficacy of nalmefene on optimizing the recovery quality of patients after general anesthesia. Methods It is a prospective, placebo-controlled, two-arm parallel groups, multicentre, double-blind, randomized (PPPMDR) clinical trial. The participants (n = 520) will be randomly assigned into two groups. Each patient will receive either: a single dose of nalmefene 0.25 µg/kg in the intervention group, or the same volume of 0.9% NaCl solution in the control group at the end of the surgery. The primary outcome will be the time interval between the end of anaesthesia and recovery endpoints achieved (Aldrete recovery score ≥ 9) in post-anesthesia care unit (PACU). The other variables are the time interval from the end of operation to extubation; Richmond Agitation Sedation Scale (RASS) score at extubation; the time at Montreal Cognitive Assessment Scale (MoCA) orientation score ≥ 5; visual analog scale (VAS) score and adverse effects including postoperative nausea and vomiting (PONV), and pruritus in PACU and 24 h postoperatively. Analysis This trial aims to study whether small dose of nalmefene can shorten the time from the end of surgery to Aldrete score ≥ 9 and improve opioid-induced side effects.This trial focuses on providing the reliable clinical evidence for satisfactory quality of recovery. Ethics and dissemination This clinical trial has been approved and supported by the ethics committee of the Renji Hospital, Shanghai Jiaotong University, School of Medicine (KY2020-150); Shanghai Tongren Hospital (2021–030-01);The First Affiliated Hospital of Guangxi Medical University (2021–032); and The First Affiliated Hospital of Zhengzhou University(2021-KY-0495–003). Analysis of the study results will be submitted to a peer-reviewed journal for publication. Trial registration ClinicalTrials.gov, NCT04713358, Registered on September 23, 2021.

show abstract

Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose

Cited by 3 publications

References 44 publications

Initial Formation of the Skin Layer of PLGA Microparticles

Initial Formation of the Skin Layer of PLGA Microparticles

Low-dose naloxone for prophylaxis of sufentanil-induced choking and postoperative nausea and vomiting

The efficacy of nalmefene on anesthetic recovery of patients: a study protocol for a multicenter randomized controlled trial

Contact Info

Product

Resources

About