scholarly journals Hyaluronic Acid-Coated Nanoparticles for the Localized Delivery of Methylprednisolone to the Injured Spinal Cord

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chao Chen ◽  
Xun Sun ◽  
Qiang Yang ◽  
Xinlong Ma

Background. The injuries associated with the spinal cord, including trauma, tumor, or disease, may lead irreparable damage leading to limited or loss of mobility, paralysis, and in extreme cases may loss senses. Methylprednisolone (MP) is often used to treat acute spinal cord injuries but suffers with high dose toxicity. The local administration of MP can overcome the neurological deficits associated with its high-dose systemic administration. Method. In the present study, we have designed a targeted delivery system hyaluronic acid- (HA-) coated polyethylenimine- (PEI-) modified poly lactic-co-glycolic acid (PLGA) nanoparticles (HA-MP-PEI-PLGA) for the localized delivery of MP. The PEI-modified PLGA (PEI-PLGA) nanoparticles were prepared and coated electrostatically by HA. The particles were well characterized using DLS and SEM analysis. The efficacy of the particles was compared with unmodified MP-PEI-PLGA nanoparticles in an in vitro and in vivo model. Results. The synthesis of PEI-PLGA was confirmed using FTIR. The HA-MP-PEI-PLGA and MP-PEI-PLGA were of size 163 ± 13   nm and 124 ± 9   nm , respectively. The major difference was observed in zeta potential of the nanoparticles where the charge reversal was observed, which was +22.6 mV and -12.9 mV, respectively, for MP-PEI-PLGA and HA-MP-PEI-PLGA. The percentage encapsulation efficiencies (EE) were calculated to be 71.4 ± 3.76 and 65.4 ± 4.71 . The synthesized nanoparticles showed the sustained release of MP which significantly reduced the proinflammatory cytokines and the lesion in HA-MP-PEI-PLGA-treated rats and enhanced the growth of axons and blood vessels; also, it reduced the production of nitric oxide. Conclusion. The results revealed that local administration of HA-MP-PEI-PLGA enhances their efficiency for effective treatment of spinal cord injury (SCI).

Author(s):  
H. Hugenholtz ◽  
D.E. Cass ◽  
M.F. Dvorak ◽  
D.H. Fewer ◽  
R.J. Fox ◽  
...  

Background:A systematic review of the evidence pertaining to methylprednisolone infusion following acute spinal cord injury was conducted in order to address the persistent confusion about the utility of this treatment.Methods:A committee of neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists engaged in active clinical practice conducted an electronic database search for articles about acute spinal cord injuries and steroids, from January 1, 1966 to April 2001, that was supplemented by a manual search of reference lists, requests for unpublished additional information, translations of foreign language references and study protocols from the author of a Cochrane systematic review and Pharmacia Inc. The evidence was graded and recommendations were developed by consensus.Results:One hundred and fifty-seven citations that specifically addressed spinal cord injuries and methylprednisolone were retrieved and 64 reviewed. Recommendations were based on one Cochrane systematic review, six Level I clinical studies and seven Level II clinical studies that addressed changes in neurological function and complications following methylprednisolone therapy.Conclusion:There is insufficient evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord injury as a treatment standard or as a guideline for treatment. Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per kilogram of body weight over fifteen minutes within eight hours of closed spinal cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of bodyweight per hour for 23 hours, is only a treatment option for which there is weak clinical evidence (Level I- to II-1). There is insufficient evidence to support extending methylprednisolone infusion beyond 23 hours if chosen as a treatment option.


1993 ◽  
Vol 4 (3) ◽  
pp. 566-572
Author(s):  
Myra F. Ellis

A spinal-cord injury can alter every aspect of a victim’s life. Despite continued improvements in mortality associated with a spinal-cord injury, until recently little progress had been made in improving neurologic function. This paper reviews the development of steroid therapy for spinal cord injuries, the mechanisms of action, and the nursing care associated with its use


1990 ◽  
Vol 72 (6) ◽  
pp. 894-900 ◽  
Author(s):  
Thomas J. Zwimpfer ◽  
Mark Bernstein

✓ The hallmark of concussion injuries of the nervous system is the rapid and complete resolution of neurological deficits. Cerebral concussion has been well studied, both clinically and experimentally. In comparison, spinal cord concussion (SCC) is poorly understood. The clinical and radiological features of 19 SCC injuries in the general population are presented. Spinal cord injuries were classified as concussions if they met three criteria: 1) spinal trauma immediately preceded the onset of neurological deficits; 2) neurological deficits were consistent with spinal cord involvement at the level of injury; and 3) complete neurological recovery occurred within 72 hours after injury. Most cases involved young males, injured during athletics or due to falls. Concussion occurred at the two most unstable spinal regions, 16 involving the cervical spinal and three the thoracolumbar junction. Fifteen cases presented with combined sensorimotor deficits, while four exhibited only sensory disturbances. Many patients showed signs of recovery with the first few hours after injury and most had completely recovered within 24 hours. Only one case involved an unstable spinal injury. There was no evidence of ligamentous instability, spinal stenosis, or canal encroachment in the remaining 18 cases. Two patients, both children, suffered recurrent SCC injuries. No delayed deterioration or permanent cord injuries occurred. Spinal abnormalities that would predispose the spinal cord to a compressive injury were present in only one of the 19 cases. This suggests that, as opposed to direct cord compression, SCC may be the result of an indirect cord injury. Possible mechanisms are discussed.


Neurosurgery ◽  
1987 ◽  
Vol 21 (2) ◽  
pp. 193-196 ◽  
Author(s):  
David H. Reines ◽  
Robert C. Harris

Abstract The records of 123 consecutive patients admitted with spinal cord injury were examined for the presence of pulmonary complications. Forty-nine had tetraplegia and 23 had paraplegia; the remainder suffered a variety of neurological deficits. Multiple injuries were encountered in 36 patients. Fifty-three pulmonary complications were noted in 44 (35.7%) patients. The most common problems were atelectasis and pneumonia. There were 22 (18%) deaths. Fourteen deaths were related to pulmonary complications. The mean age of patients who died was 52 ± 13 (SE) compared to 28 ± 12 for survivors. A mean forced vital capacity (FVC) of 1127 ± 410 cc in patients suffering respiratory difficulties compared to a FVC of 1865 ± 85 cc in patients without complications (P < 0.001). Oxygenation (PaO2 90 ± 19 torr) was normal in patients without respiratory problems and was abnormal in patients developing problems (PaO2 76 ± 30 torr; P < 0.05). Twenty patients were treated with a rotating bed. The complication rate of patients on the bed was only 10%. In conclusion, respiratory problems remain a significant cause of morbidity and mortality in spinal cord injury. The forced vital capacity, blood oxygen tension, and age are predictors of pulmonary complications. The use of a multidisciplinary approach and a rotating bed may minimize these problems.


2016 ◽  
Vol 60 (2) ◽  
pp. 41-46 ◽  
Author(s):  
I. Šulla ◽  
V. Balik ◽  
J. Petrovičová ◽  
V. Almášiová ◽  
K. Holovská ◽  
...  

Abstract Spinal cord injuries (SCI) with their tragic consequences belong to the most serious pathological conditions. That is why they have stimulated basic research workers, as well as health care practitioners, to search for an effective treatment for decades. Animal experimental models have been essential in these efforts. We have jointly decided to test and standardize one of the spinal cord injury compression models in rats. Twentythree adult female Wistar rats weighing 250-320 g were utilized. Employing general anaesthesia along with a mixture of sevoflurane with O2, 2 rats (sham controls) had their vertebral arch of either Th8 or Th9 vertebra removed (laminectomy). The other 21 experimental rats with similar laminectomies were divided into 3 subgroups (n = 7) which received compression impact forces of 30, 40 or 50 g (subgroups-1, -2, and -3, respectively) applied on their exposed spinal medulla for 15 minutes. All rats were observed for 28 days after the experimental procedure and their motor functions were assessed by the Basso, Beattie, Bresnahan (BBB) test 6 hours, 7, 21 and 28 days after the simulated SCI. All 23 rats survived the surgical procedures. The control rats were without any neurological deficits. There were, in every experimental subgroup, 1 or 2 rats with extreme BBB scores. So the rats with the maximum and minimum BBB values were excluded. Then, the results acquired in the residual 5 rats in each group were averaged and statistically analysed by the Tukey multiple comparisons test. Statistically significant intersubgroup differences were found at all survival times equal to or longer than 7 post SCI days. The goal of the SCI experiment was to generate a reproducible and reliable, submaximal spinal cord trauma model. The statistical analyses demonstrated that this objective was best achieved in the subgroup-2 with the 40 g compression.


2017 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Tochukwu C. Ikpeze ◽  
Addisu Mesfin

Spinal cord injuries (SCIs) are sustained by more than 12 500 patients per year in the United States and more globally. The SCIs disproportionately affect the elderly, especially men. Approximately 60% of these injuries are sustained traumatically through falls, but nontraumatic causes including infections, tumors, and medication-related epidural bleeding have also been documented. Preexisting conditions such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis can render the spine stiff and are risk factors as well as cervical spondylosis and ensuing cervical stenosis. Treatment options vary depending on the severity, location, and complexity of the injury. Surgical management has been growing in popularity over the years and remains an option as it helps reduce spinal cord compression and alleviate pain. Elevating mean arterial pressures to prevent spinal cord ischemia and avoiding the second hit of SCI have become more common as opposed to high dose steroids. Ongoing clinical trials with pharmacological agents such as minocycline and riluzole have shown early, promising results in their ability to reduce cellular damage and facilitate recovery. Though SCI can be life changing, the available treatment options have aimed to reduce pain and minimize complications and maintain quality of life alongside rehabilitative services.


2017 ◽  
Vol 20 (6) ◽  
pp. 567-574 ◽  
Author(s):  
Michelle C. Caruso ◽  
Margot C. Daugherty ◽  
Suzanne M. Moody ◽  
Richard A. Falcone ◽  
Karin S. Bierbrauer ◽  
...  

OBJECTIVEMethylprednisolone sodium succinate (MPSS) has been studied as a pharmacological adjunct that may be given to patients with acute spinal cord injury (ASCI) to improve neurological recovery. MPSS treatment became the standard of care in adults despite a lack of evidence supporting clinical benefit. More recently, new guidelines from neurological surgeon groups recommended no longer using MPSS for ASCI, due to questionable clinical benefit and known complications. However, little information exists in the pediatric population regarding MPSS use in the setting of ASCI. The aim of this paper was to describe steroid use and side effects in patients with ASCI at the authors’ Level 1 pediatric trauma center in order to inform other hospitals that may still use this therapy.METHODSA retrospective chart review was conducted to determine adherence in ordering and delivery according to the guideline of the authors’ institution and to determine types and frequency of complications. Inclusion criteria included age < 17 years, blunt trauma, physician concern for ASCI, and admission for ≥ 24 hours or treatment with high-dose intravenous MPSS. Exclusion criteria included penetrating trauma, no documentation of ASCI, and incomplete medical records. Charts were reviewed for a predetermined list of complications.RESULTSA total of 602 patient charts were reviewed; 354 patients were included in the study. MPSS was administered in 59 cases. In 34 (57.5%) the order was placed correctly. In 13 (38.2%) of these 34 cases, MPSS was administered according to the recommended timeline protocol. Overall, only 13 (22%) of 59 patients received the therapy according to protocol with regard to accurate ordering and administration.Among the patients with ASCI, 20 (55.6%) of the 36 who received steroids had complications, which was a significantly higher rate than in those who did not receive steroids (8 [24.2%] of 33, p = 0.008). Among the patients without ASCI, 10 (43.5%) of the 23 who received steroids also experienced significantly more complications than patients who did not receive steroids (50 [19.1%] of 262, p = 0.006).CONCLUSIONSHigh-dose MPSS for ASCI was not delivered to pediatric patients according to protocol with a high degree of reliability. Patients receiving steroids for pediatric ASCI were significantly more likely to experience complications than patients not receiving steroids. The findings presented, including complications of steroid use, support removal of high-dose MPSS as a treatment option for pediatric ASCI.


2021 ◽  
Vol 2 (4) ◽  
pp. 409-415
Author(s):  
Slaviša Zagorac

Spinal cord injuries represent a major challenge in terms of current concepts of treatment. This condition is frequently associated with long term therapy in addition to a greater incidence of early and late complications. The goal of treatment is to alleviate pressure on the spinal cord caused by hematomas or bone fragments, in the shortest time possible. Hence, surgical decompression of the spinal cord is the first line of treatment, in cases where this approach is indicated. Apart from invasive methods, treatment also consists of the use of various pharmacological agents, whose therapeutic goal is to decrease edema and inflammation, especially in the first several days following injury. One of the most commonly administered drugs in such cases is methylprednisolone, however, controversy with regards to the timing of its administration and proper dosing, still exists. This drug has been in use for decades in the treatment of spinal cord injuries with various protocols having been introduced and revised overtime. The aim of this article is to showcase the current understanding of the use of corticosteroids in acute spinal cord injuries. The most significant protocols in use today for the administration of methylprednisolone (National Acute Spinal Cord Injury Studies-NASCIS I, II and III), along with a brief overview of pertinent literature, are discussed in this paper. Analysis of the available data suggests that the use of methylprednisolone in spinal cord injuries is still highly controversial due to the inconclusive relationship between the therapeutic benefits and the risk of side effects. The current understanding is that the use of the drug is justified in the first eight hours following injury, especially in cases involving incomplete neurological deficits, more specifically quadriparesis and paraparesis.


2014 ◽  
Vol 37 (1) ◽  
pp. E13 ◽  
Author(s):  
Eduardo Martinez-del-Campo ◽  
Leonardo Rangel-Castilla ◽  
Hector Soriano-Baron ◽  
Nicholas Theodore

Object Performance of MR imaging in patients with gunshot wounds at or near the lumbar spinal canal is controversial. The authors reviewed the literature on the use of MR imaging in gunshot wounds to the spine. They discuss the results from in vitro and clinical studies, analyze the physical properties of common projectiles, and evaluate the safety and indications for MR imaging when metallic fragments are located near the spinal canal. Methods A review of the English-language literature was performed. Data from 25 articles were analyzed, including 5 in vitro studies of the interaction between 95 projectiles and the MR system's magnetic fields, and the clinical outcomes in 22 patients with metallic fragments at or near the spinal canal who underwent MR imaging. Results Properties of 95 civilian and military projectiles were analyzed at a magnet strength of 1, 1.5, 3, and 7 T. The most common projectiles were bullets with a core of lead, either with a copper jacket or unjacketed (73 [76.8%] of 95). Steel-containing (core or jacket) projectiles comprised 14.7%. No field interaction was evident in 78 (96.3%) of the 81 nonsteel projectiles. All steel projectiles showed at least positive deflection forces, longitudinal migration, or rotation. Heating of the projectiles was clinically insignificant. Image artifact was significant in all 9 steel bullets tested, but was not significant in 39 (88.6%) of the 44 nonsteel bullets tested. Overall, 22 patients with complete (82%) and incomplete (14%) spinal cord injury secondary to a projectile lodged inside the spinal canal underwent MR imaging. Discomfort and further physical or neurological deficits were not reported by any patient. Two patients with spinal cord injuries underwent MR imaging studies before surgical decompression and had subsequent, significant neurological improvement. Conclusions Metallic implants near or at the spinal canal are a relative contraindication for MR imaging. However, safe MR imaging might be feasible when a projectile's properties and a patient's individualized clinical presentation are considered.


2013 ◽  
Vol 2 (1) ◽  
pp. 81-85
Author(s):  
Abdul Qodir

Acute spinal cord injury is a devastating condition typically affecting young people, mostly males. High-Dose Methylprednisolone treatment in the early hours after the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient’s life. The aim To review randomized trials of High-Dose Methylprednisolone in Acute Spinal Cord Injuries. All randomized controlled trials of steroid treatment for acute spinal cord injury in any language. Data have been extracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. The evidence produced by this systematic review support the use of high dose methylprednisolone in acute spinal cord injury to improve neurological recovery. Patients who received high-dose methylprednisolone therapy should be observed with intensive in order to reduce complications from such therapy.


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