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1.
Curr Opin Anaesthesiol ; 36(2): 168-175, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36550092

RESUMEN

PURPOSE OF REVIEW: The incorporation of point of care ultrasound into the field of anesthesiology and perioperative medicine is growing at rapid pace. The benefits of this modality align with the acuity of patient care and decision-making in anesthetic care of a trauma patient. RECENT FINDINGS: Cardiac ultrasound can be used to diagnose cardiac tamponade or investigate the inferior vena cava to assess volume status in patients who may suffer from hemorrhagic shock. Thoracic ultrasound may be used to rapidly identify pneumothorax or hemothorax in a patient suffering chest wall trauma. In addition, investigators are exploring the utility of ultrasonography in traumatic airway management and elevated intracranial pressure. In addition, the utility of gastric ultrasound on trauma patients is briefly discussed. SUMMARY: Incorporation of point of care ultrasound techniques into the practice of trauma anesthesiology is important for noninvasive, mobile and expeditious assessment of trauma patients. In addition, further large-scale studies are needed to investigate how point of care ultrasound impacts outcomes in trauma patients.


Asunto(s)
Anestesiología , Sistemas de Atención de Punto , Humanos , Ultrasonografía/métodos , Ecocardiografía , Anestesiología/métodos , Atención Perioperativa/métodos
2.
Cureus ; 16(7): e64981, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39161486

RESUMEN

Scrub typhus is caused by Orientia tsutsugamushi, a Gram-negative coccobacillus. It comprises three strains: Karp, Gilliam, and Kato. Cases of scrub typhus are usually found in the Asia-Pacific region, and their presentation may range from minimal symptoms to multi-organ involvement, with or without the presence of an eschar mark. Varying manifestations of scrub typhus, such as gangrene, meningoencephalitis, anemia with jaundice, and hematuria, have been observed. In the Kumaun region of northern India, there has been a surge in the number of scrub typhus cases. Typically, this disease is accompanied by an eschar mark, but occasionally it can manifest without one. We report a series of four cases presenting with various unusual symptoms such as gangrene of the limbs, meningoencephalitis, jaundice, and hematuria. Serology for scrub typhus should be considered in all patients with acute febrile illness not responding to treatment, especially in mountainous regions, to prevent the associated mortality.

3.
J Vis Exp ; (209)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39141561

RESUMEN

Frailty is a significant predictor of a range of adverse outcomes in surgical patients, including increased mechanical ventilation time, longer hospital stays, unplanned readmissions, stroke, delirium, and death. However, accessible tools for screening in clinical settings are limited. Computed tomography of the psoas muscle is the current standard imaging device for measuring frailty, but it is expensive, time-consuming, and exposes the patient to ionizing radiation. Recently, the use of point-of-care ultrasound (POCUS) has emerged as a potential tool to determine the presence of frailty and has been shown to accurately predict frailty and postoperative outcomes. In this article, we will describe the image acquisition of the quadriceps muscles and explain how they can be used to determine frailty and predict postoperative adverse events. We will present information on probe selection, patient positioning, and troubleshooting. Images from a demonstration will be used to present the POCUS technique and example results. The article will culminate in a discussion of the use of these images in medical decision-making and potential limitations.


Asunto(s)
Fragilidad , Sistemas de Atención de Punto , Ultrasonografía , Humanos , Ultrasonografía/métodos , Fragilidad/diagnóstico por imagen , Músculo Cuádriceps/diagnóstico por imagen , Anciano
4.
Cureus ; 15(6): e40572, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37465778

RESUMEN

Sudden infant death syndrome (SIDS) continues to be one of the top causes of infant death in the U.S. Despite significant public health initiatives focused on high-risk populations to enhance sleep environments and techniques. The SIDS rate has remained stable in recent years. Risk factors and newer risk reduction strategies for SIDS are the focus of this review article. We conducted a comprehensive literature search on Medline, Cochrane, Embase, and Google Scholar until July 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "SIDS," "Sudden Infant Death" and "SUID". We explored the literature on SIDS for its epidemiology, pathophysiology, the role of various etiologies and their influence, associated complications leading to SIDS, and preventive and treatment modalities. Despite a more than 50% drop-in rates since the start of the "Back to Sleep" campaign in 1994, sudden infant death syndrome (SIDS) continues to be the top cause of post-neonatal mortality in the United States, despite continued educational initiatives that support safe sleep and other risk reduction strategies. The new American Academy of Pediatrics guidelines for lowering the risk of SIDS include a lot of emphasis on sleeping habits, bedding, and environment but also include elements that are frequently ignored (i.e., prenatal care, smoking, alcohol and drug use, and childhood vaccinations). This study highlights these less-frequently discussed aspects and identifies treatments that have produced beneficial behavioral shifts that benefit newborns as well as their mothers' health and wellbeing.

5.
J Vis Exp ; (199)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37811946

RESUMEN

Over the past two decades, diagnostic point-of-care ultrasound (POCUS) has emerged as a rapid and non-invasive bedside tool for addressing clinical inquiries related to gastric content. One emerging concern pertains to patients about to undergo sedation and/or endotracheal intubation: the elevated risk of aspiration from the patient's stomach contents. Aspiration of gastric contents into the lungs poses a serious and potentially life-threatening complication. This occurs more frequently when the stomach is considered "full" and can be affected by the techniques employed for airway management, making it potentially preventable. To mitigate the risk of peri-procedural aspiration, two distinct medical specialties (anesthesiology and critical care medicine) have independently developed techniques to utilize ultrasonography for identifying patients requiring "full stomach" precautions. Due to these separate specialties, the work of each group remains relatively unfamiliar outside its respective field. This article presents descriptions of both techniques for gastric ultrasound. Furthermore, it explains how these approaches can complement each other when one of them falls short. Regarding image acquisition, the article covers the following topics: indications and contraindications, selection of the appropriate probe, patient positioning, and troubleshooting. The article also delves into image interpretation, complete with example images. Additionally, it demonstrates how one of the two techniques can be employed to estimate gastric fluid volume. Lastly, the article briefly discusses medical decision-making based on the findings of this examination.


Asunto(s)
Anestesia , Sistemas de Atención de Punto , Humanos , Adulto , Estómago/diagnóstico por imagen , Ultrasonografía/métodos , Pruebas en el Punto de Atención
6.
J Neurosurg Anesthesiol ; 35(2): 201-207, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-34881561

RESUMEN

BACKGROUND: An external ventricular drain (EVD) training module may improve the knowledge and proficiency of perioperative health care providers (HCPs). METHODS: We examined knowledge gaps, self-reported comfort in managing EVDs, and improvement in self-assessment scores among HCPs from 7 academic medical centers based on an online EVD training module. RESULTS: Of the 326 HCPs who completed the module, 207 (70.6%) reported being uncomfortable managing EVDs. The median pretest scores were 6 (interquartile range=2), and posttest scores were 8 (interquartile range=1), out of a maximum possible score of 9. The most frequent incorrectly answered questions were: (a) maximum allowed hourly cerebrospinal fluid volume drainage (51%), (b) the components of a normal intracranial pressure waveform (41%), and (c) identifying the correct position of the stopcock for accurate measurement of intracranial pressure (41%). The overall gain in scores was 2 (interquartile range=2) and highest among HCPs who had managed 1 to 25 EVDs (2.51, 95% confidence interval: 2.23-2.80), and without self-reported comfort in managing EVDs (2.26, 95% confidence interval: 1.96-2.33, P <0.0001). The majority of participants (312, 95.7%) reported that the training module helped them understand how to manage EVDs, and 276 (84.7%) rated the module 8 or more out of 10 in recommending it to their colleagues. CONCLUSIONS: This online EVD training module was well-received by participants. Overall, improved scores reflect enhanced knowledge among HCPs following completion of the module. The greatest benefit was observed in those reporting less experience and feeling uncomfortable in managing EVDs. The impact on the reduction in EVD-associated adverse events deserves further examination.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo , Drenaje , Humanos , Estudios Retrospectivos , Drenaje/métodos , Presión Intracraneal , Ventriculostomía/métodos
7.
Artículo en Inglés | MEDLINE | ID: mdl-37192477

RESUMEN

BACKGROUND: The aim of this survey was to understand institutional spine surgery practices and their concordance with published best practices/recommendations. METHODS: Using a global internet-based survey examining perioperative spine surgery practice, reported institutional spine pathway elements (n=139) were compared with the level of evidence published in guideline recommendations. The concordance of clinical practice with guidelines was categorized as poor (≤20%), fair (21%-40%), moderate (41%-60%), good (61%-80%), or very good (81%-100%). RESULTS: Seventy-two of 409 (17.6%) institutional contacts started the survey, of which 31 (7.6%) completed the survey. Six (19.4%) of the completed surveys were from respondents in low/middle-income countries, and 25 (80.6%) were from respondents in high-income countries. Forty-one incomplete surveys were not included in the final analysis, as most were less than 40% complete. Five of 139 (3.6%) reported elements had very good concordance for the entire cohort; hospitals with spine surgery pathways reported 18 elements with very good concordance, whereas institutions without spine surgery pathways reported only 1 element with very good concordance. Reported spine pathways included between 7 and 47 separate pathway elements. There were 87 unique elements in the reviewed pathways. Only 3 of 87 (3.4%) elements with high-quality evidence demonstrated very good practice concordance. CONCLUSIONS: This global survey-based study identified practice variation and low adoption rates of high-quality evidence in the care of patients undergoing complex spine surgery.

8.
Curr Anesthesiol Rep ; 12(2): 217-225, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35075351

RESUMEN

Purpose of Review: With advances in technology and availability of handheld ultrasound probes, studies are focusing on the perioperative care of patients, but a limited number specifically on trauma patients. This review highlights recent findings from studies using point of care ultrasound (POCUS) to improve the care of trauma patients. Recent Findings: Major findings include the use of POCUS to assess volume status of trauma patients upon arrival to measure the major vasculature. Additionally, several studies have advanced the use of POCUS to identify pneumothorax in trauma patients. Finally, the ASA POCUS certification and ASRA expert guidelines are examples of international organizations establishing guidelines for utilization and training of anesthesiologists in the field of POCUS, which will be discussed. Summary: Despite the COVID-19 pandemic, and considerable resources being diverted to fight this global healthcare crisis, advances are being made in utilization of POCUS to aid the care of trauma patients.

9.
J Vis Exp ; (187)2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36282685

RESUMEN

With its increasing popularity and accessibility, portable ultrasonography has been rapidly adapted not only to improve the perioperative care of patients, but also to address the potential benefits of employing ultrasound in airway management. The benefits of point of care ultrasound (POCUS) include its portability, the speed at which it can be utilized, and its lack of invasiveness or exposure of the patient to radiation of other imaging modalities. Two primary indications for airway POCUS include confirmation of endotracheal intubation and identification of the cricothyroid membrane in the event a surgical airway is required. In this article, the technique of using ultrasound to confirm endotracheal intubation and the relevant anatomy is described, along with the associated ultrasonographic images. In addition, identification of the anatomy of the cricothyroid membrane and the ultrasonographic acquisition of appropriate images to perform this procedure are reviewed. Future advances include utilizing airway POCUS to identify patient characteristics that might indicate difficult airway management. Traditional bedside clinical exams have, at best, fair predictive values. The addition of ultrasonographic airway assessment has the potential to improve this predictive accuracy. This article describes the use of POCUS for airway management, and initial evidence suggests that this has improved the diagnostic accuracy of predicting a difficult airway. Given that one of the limitations of airway POCUS is that it requires a skilled sonographer, and image analysis can be operator dependent, this paper will provide recommendations to standardize the technical aspects of airway ultrasonography and promote further research utilizing sonography in airway management. The goal of this protocol is to educate researchers and medical health professionals and to advance the research in the field of airway POCUS.


Asunto(s)
Laringe , Sistemas de Atención de Punto , Humanos , Ultrasonografía/métodos , Manejo de la Vía Aérea/métodos , Intubación Intratraqueal , Laringe/diagnóstico por imagen
10.
Proc (Bayl Univ Med Cent) ; 35(5): 604-607, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35991745

RESUMEN

Measurement of the lateral parapharyngeal wall has been shown to correlate with severity of obstructive sleep apnea, which is believed to increase risk of difficulty in mask ventilation (MV). This study aimed to assess the efficacy of using ultrasound to measure the lateral parapharyngeal wall thickness (LPWT) to predict the difficulty of MV. The LPWT was measured as the distance between the inferior border of the carotid artery and the lateral wall of the pharynx. Difficulty of MV was assessed according to an MV scale. A total of 92 patients were enrolled. Measurements of the LPWT ranged from 1.52 to 4.43 cm. There was a significant correlation between LPWT and difficulty of MV (P = 0.004). Every increase in 1 cm of LPWT was associated with an odds of increase in MV score of 3.17 (P < 0.05). With a cutoff of 3.5 cm, the area under the curve for LPWT was 0.67. The negative predictive value was 0.89, and the positive predictive value was 0.57. Use of point-of-care ultrasound to measure the LPWT shows promise in its ability to aid in airway management planning. Ultrasonic measurements of the LPWT have reasonable accuracy for predicting difficulty of MV.

11.
J Neurosurg Anesthesiol ; 34(3): 257-276, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34483301

RESUMEN

Evidence-based standardization of the perioperative management of patients undergoing complex spine surgery can improve outcomes such as enhanced patient satisfaction, reduced intensive care and hospital length of stay, and reduced costs. The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) tasked an expert group to review existing evidence and generate recommendations for the perioperative management of patients undergoing complex spine surgery, defined as surgery on 2 or more thoracic and/or lumbar spine levels. Institutional clinical management protocols can be constructed based on the elements included in these clinical practice guidelines, and the evidence presented.


Asunto(s)
Anestesiología , Cuidados Críticos , Humanos , Vértebras Lumbares , Procedimientos Neuroquirúrgicos , Atención Perioperativa
12.
J Trauma Acute Care Surg ; 93(1): 43-51, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35393379

RESUMEN

BACKGROUND: Blood-based balanced resuscitation is a standard of care in massively bleeding trauma patients. No data exist as to when this therapy no longer significantly affects mortality. We sought to determine if there is a threshold beyond which further massive transfusion will not affect in-hospital mortality. METHODS: The Trauma Quality Improvement database was queried for all adult patients registered between 2013 and 2017 who received at least one unit of blood (packed red blood cell) within 4 hours of arrival. In-hospital mortality was evaluated based on the total transfusion volume (TTV) at 4 hours and 24 hours in the overall cohort (OC) and in a balanced transfusion cohort, composed of patients who received transfusion at a ratio of 1:1 to 2:1 packed red blood cell to plasma. A bootstrapping method in combination with multivariable Poisson regression was used to find a cutoff after which additional transfusion no longer affected in-hospital mortality. Multivariable Poisson regression was used to control for age, sex, race, highest Abbreviated Injury Scale score in each body region, comorbidities, advanced directives limiting care, and the primary surgery performed for hemorrhage control. RESULTS: The OC consisted of 99,042 patients, of which 28,891 and 30,768 received a balanced transfusion during the first 4 hours and 24 hours, respectively. The mortality rate plateaued after a TTV of 40.5 units (95% confidence interval [CI], 40-41) in the OC at 4 hours and after a TTV of 52.8 units (95% CI, 52-53) at 24 hours following admission. In the balanced transfusion cohort, mortality plateaued at a TTV of 39 units (95% CI, 39-39) and 53 units (95% CI, 53-53) at 4 hours and 24 hours following admission, respectively. CONCLUSION: Transfusion thresholds exist beyond which ongoing transfusion is not associated with any clinically significant change in mortality. These TTVs can be used as markers for resuscitation timeouts to assess the plan of care moving forward. LEVEL OF EVIDENCE: Prognostic and epidemiological, Level III.


Asunto(s)
Transfusión Sanguínea , Heridas y Lesiones , Escala Resumida de Traumatismos , Adulto , Hemorragia/etiología , Hemorragia/terapia , Mortalidad Hospitalaria , Humanos , Plasma , Resucitación/métodos , Estudios Retrospectivos , Heridas y Lesiones/terapia
13.
Int J Biol Macromol ; 189: 100-113, 2021 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-34411613

RESUMEN

In the present work, lactoferrin (Lf) based nanoparticle incorporated self-supporting gel encapsulating a flavonoid, quercetin (Q), was developed. The complex formation between Lf and Q was assessed using molecular docking and dynamics simulation that lactoferrin and quercetin showed strong interaction and binding supporting hydrophobic interaction. The microscopic, spectroscopic, and x-ray techniques were used to characterize the gel extensively. In vitro drug release was studied to understand the release pattern of quercetin from the protein gel. The viscosity of the gel and its rheological characteristics were determined using a Brookfield viscometer. Ex vivo skin permeation studies using vertical diffusion cells were carried out to understand its skin permeation properties. The gel showed strong anti-oxidant activity using the DPPH scavenging assay. The enhanced effect of the Lf-Q complex on antioxidant enzyme activity (superoxide dismutase, catalase, and malondialdehyde), was supported by molecular dynamics, surface hydrophobicity, and in vitro studies. To investigate the effect of the gel on angiogenesis, the chorioallantoic membrane assay was performed and its compatibility with erythrocytes was also assessed. Suitability for topical administration was assessed using skin irritation studies performed on Sprague Dawley rats. The overall results suggest that the developed NiPG is suitable for cutaneous localization of quercetin with enhanced antioxidant activity.


Asunto(s)
Geles/química , Lactoferrina/química , Simulación de Dinámica Molecular , Nanopartículas/química , Estrés Oxidativo , Polifenoles/química , Células 3T3 , Animales , Antioxidantes/farmacología , Bovinos , Supervivencia Celular/efectos de los fármacos , Pollos , Membrana Corioalantoides/efectos de los fármacos , Liberación de Fármacos , Eritrocitos/efectos de los fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Ligandos , Masculino , Ratones , Simulación del Acoplamiento Molecular , Quercetina/química , Ratas Sprague-Dawley , Piel/efectos de los fármacos , Pruebas de Irritación de la Piel , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Viscosidad , Difracción de Rayos X
14.
J Emerg Trauma Shock ; 14(4): 216-221, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35125787

RESUMEN

INTRODUCTION: Pregnant trauma patients are an underdescribed cohort in the medical literature. Noting injury patterns and contributors to mortality may lead to improved care. METHODS: Female patients between 14 and 49 years of age were identified among entries in the 2017 National Trauma Data Bank. Data points were compared using Chi-square test, Fisher's exact test, Student's t-test, Mann-Whitney rank-sum, or multiple logistic regression as appropriate. P < 0.05 was used to determine the findings of significance. RESULTS: There were 569 pregnant trauma patients identified, which was 0.54% of the 105,507 women identified. Overall, mortality was low among all women and not different between groups (1.2% for pregnant women vs. 2.2% for nonpregnant, P = 0.12). Pregnant women with head injuries had a higher mortality rate than pregnant women without (4.2% vs. 0.47%, P < 0.01). Head injuries (Abbreviated Injury Severity Score [AIS] head >1) were associated with an increased risk for mortality (odds ratio: 3.33, 95% confidence interval: 3.0-3.7, P < 0.01). CONCLUSION: There was no increase in mortality for trauma patients who are pregnant when controlling for covariates. Factors such as head injuries, the need for blood, and comorbid diseases appear to have a more significant contribution to mortality. We also report the prevalence of head, cervical spine, and extremity injuries in pregnant trauma patients. Multidisciplinary simulation, jointly crafted protocols, and expanding training in regional anesthesia may be the next steps to improving care for pregnant trauma patients.

15.
Int J Biol Macromol ; 178: 444-463, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33636277

RESUMEN

In the present study, we have developed the core-shell metal organic framework (MOF) of zinc, wherein titanocene dichloride (TC) loaded lactoferrin (Lf) functioned as a core. The complexation of TC to Lf was studies using molecular dynamics study, Quantum mechanical model and spectroscopic investigations. Plackett-Burman design was used to screen and select the critical factors affecting the responses (size, zeta potential and PDI) while the effect of those parameter on the quality attributes (size and yield) was studied by means of a Box-Behnken design. The optimised Lf-TC nanoparticles were loaded inside the ZIF-8 framework along with an anticancer agent 5 Fluorouracil and characterized using techniques like FTIR, PXRD, Raman spectroscopy, EDX and UV-NIR spectroscopy and morphological techniques like SEM, TEM, AFM. The compatibility of the loaded ZIF-8 framework was examined by haemocompatibility studies. The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in-vivo administration in Wistar rats. Therefore, we can conclude that by employing the approach of DOE we were able to optimize the size and yield of Lf-TC NPs and further by loading inside ZIF-8 framework along with an anticancer drug like 5 fluorouracil we were able to develop a potential nanoplatform for the multimodal therapy of Neuroblastoma.


Asunto(s)
Antineoplásicos , Fluorouracilo , Imidazoles , Estructuras Metalorgánicas , Simulación de Dinámica Molecular , Nanopartículas , Neuroblastoma , Compuestos Organometálicos , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/química , Antineoplásicos/farmacología , Fluorouracilo/efectos adversos , Fluorouracilo/química , Fluorouracilo/farmacología , Imidazoles/efectos adversos , Imidazoles/química , Imidazoles/farmacología , Estructuras Metalorgánicas/efectos adversos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/metabolismo , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Ratas , Ratas Wistar
16.
Anesthesiol Clin ; 38(2): 297-310, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32336385

RESUMEN

Sex plays a role in all stages of the organ transplant process, including listing, sex/size matching of organs, complications, graft survival, and mortality. Sex-related differences in organ transplantation are likely multifactorial related to biological and social characteristics. More information is needed to determine how sex-related differences can lead to improved outcomes for future donors and recipients of solid organs. This article provides an overview on the impact of sex on various types of solid organ transplant, including kidney, pancreas, liver, lung, and heart transplants.


Asunto(s)
Trasplante de Órganos , Atención Perioperativa , Femenino , Humanos , Masculino , Trasplante de Órganos/efectos adversos , Complicaciones Posoperatorias/etiología , Caracteres Sexuales , Obtención de Tejidos y Órganos
17.
Int J Pharm ; 588: 119735, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32763386

RESUMEN

Multimodal therapeutic approach has been gaining lot of attention for effective therapy of cancer. In the present work, a novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. Lactoferrin (Lf) has been used as protein matrix for loading titanocene which was then enclosed in ZIF-8 framework along with 5-FU (ZIF-8@Lf-TC). The ZIF-8 was further coated with Lenalidomide-HA conjugate linked via hydrazone linkage (LND-HA@ZIF-8@Lf-TC). The developed nanocomposite was extensively characterized using spectroscopic, x-ray and electron microscopic techniques. The nanocomposites were evaluated for pH responsive drug release, stability, bio-interaction, and haemocompatibility which confirmed pH responsive nature of nanocomposite, stability and absence of any significant interaction with biomolecules. In obtained results for in vitro cell line studies performed in U87MG and RAW264.7 cells demonstrated enhanced cell cytotoxicity against cancer cells which was further supported by results of cellular ROS generation and surface ROS generation by nanocomposites. The Zinc and Lf mediated disruption of intracellular IL-6 and TNFα levels was observed with synthesized nanocomposites. They demonstrated pH responsive release of 5-FU and LND along with sustained release of both drugs in simulated medium. The LND-HA@ZIF-8@Lf-TC demonstrated superior cell growth supressing ability compared to ZIF-8@Lf-TC and ZIF-8. The nanocomposites were stable in biomimicking environment as well as did not show any significant interaction with RBC, plasma or CSF. The overall results suggest that LND-HA@ZIF-8@Lf-TC can be explored as promising platform for dual drug delivery mediated multimodal therapy of cancer.


Asunto(s)
Glioblastoma , Ácido Hialurónico , Preparaciones Farmacéuticas , Doxorrubicina , Liberación de Fármacos , Glioblastoma/tratamiento farmacológico , Humanos , Concentración de Iones de Hidrógeno
18.
Adv Healthc Mater ; 9(14): e2000465, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32543010

RESUMEN

Atherosclerosis is a chronic disease that can lead to life-threatening events such as myocardial infarction and stroke, is characterized by the build-up of lipids and immune cells within the arterial wall. It is understood that inflammation is a hallmark of atherosclerosis and can be a target for therapy. In support of this concept, an injectable nanoliposomal formulation encapsulating fluocinolone acetonide (FA), a corticosteroid, is developed that allows for drug delivery to atherosclerotic plaques while reducing the systemic exposure to off-target tissues. In this study, FA is successfully incorporated into liposomal nanocarriers of around 100 nm in size with loading efficiency of 90% and the formulation exhibits sustained release up to 25 d. The anti-inflammatory effect and cholesterol efflux capability of FA-liposomes are demonstrated in vitro. In vivo studies carried out with an apolipoprotein E-knockout (Apoe-/- ) mouse model of atherosclerosis show accumulation of liposomes in atherosclerotic plaques, colocalization with plaque macrophages and anti-atherogenic effect over 3 weeks of treatment. This FA-liposomal-based nanocarrier represents a novel potent nanotherapeutic option for atherosclerosis.


Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Animales , Apolipoproteínas E , Aterosclerosis/tratamiento farmacológico , Liposomas , Macrófagos , Ratones , Ratones Noqueados , Placa Aterosclerótica/tratamiento farmacológico
19.
Pharmaceutics ; 11(7)2019 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-31336771

RESUMEN

Diseases affecting the posterior segment of the eye such as age-related macular degeneration and diabetic retinopathy are leading causes of blindness all over the world. The current treatment regimen for such diseases involves repeated intravitreal injections of anti- Vascular Endothelial Growth Factor (VEGF) proteins. This method is highly invasive and can lead to severe complications. In an attempt to develop less invasive alternatives, we propose the use of a controlled release system consisting of anti-VEGF loaded hollow microcapsules that can be administered periocularly to form drug eluting depots on the episcleral surface. The microcapsules with either positive or negative surface charge were prepared by a layer by layer approach and showed pH responsive permeability switching. An ex vivo experiment using porcine sclera indicated positively charged microcapsules remained on the episcleral surface over four days while the negatively charged microcapsules were washed away. These positively charged microcapsules were then loaded with anti-VEGF protein ranibizumab using pH dependent permeability switching and protein release from the microcapsules were studied using an in vitro setup. An ex vivo experiment utilizing porcine sclera demonstrated sustained release of ranibizumab over seven days with zero-order kinetics.

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