Lipid-based nanoformulations in the treatment of neurological disorders

Abstract

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson’s. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood–brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.     

Patients’ anxiety around incidental brain tumors: a qualitative study

Background

Incidental findings are common on MRI. Our study examined how patients are told about their incidental finding as well as anxiety until the neurosurgical consultation and afterward.

Methods

Qualitative research methodology was used. Thirty-two participants were interviewed using open-ended questions. Answers were transcribed and analyzed for themes.

Results

The level of patient satisfaction for the initial breaking of the news averaged 4.1 (range 1–5). Four themes were identified: (1) emotional stress over incidental findings are partially dependent on how the news was communicated; (2) breaking worrisome news is best done in person, but telephone communication can sometimes be acceptable; (3) patients are divided about how much information they wish to get about incidental findings before going for an MRI; (4) waiting for the neurosurgical consultation is a stressful time without adequate support.

Conclusions

When dealing with an unexpected MRI finding, patients are anxious about the situation. Our study exposes ways the experience could be made more comfortable for patients right from the start, from being told the news in a calm and sympathetic manner, to providing support for patients while they wait for a meeting with a neurosurgeon, to expediting the neurosurgical consultation.     

Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[¹⁸F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.     

Minimally Invasive Approaches Do Not Compromise Outcomes for Pneumonectomy: A Comparison Using the National Cancer Database

Introduction

Minimally invasive approaches are increasingly being used for the conduct of complex surgical procedures. Whether the benefits of minimally invasive approaches compared to thoracotomy for sublobar and lobar lung resection for NSCLC are realized for patients undergoing pneumonectomy is not clear.

Incidence and impact of postoperative atrial fibrillation after minimally invasive esophagectomy

Atrial fibrillation (AF) following open esophagectomy has been associated with increased rates of pulmonary and anastomotic complications, and mortality. This study seeks to evaluate effects of AF after minimally invasive esophagectomy (MIE). A retrospective review of patients consecutively treated with MIE for esophageal carcinoma, dysplasia. and benign disease from November 2006 to November 2011 was performed. One hundred twenty‐one patients underwent MIE. Median age was 65 years (range 26–88) with 85% being male. Thirty‐eight (31.4%) patients developed AF postoperatively. Of these 38 patients, 7 (18.4%) had known AF preoperatively. Patients with postoperative AF were significantly older than those without postoperative AF (68.7 vs. 62.8 years, P = 0.008) and more likely to be male (94.7% vs. 80.7%, P = 0.04). Neoadjuvant chemoradiation showed a trend toward increased risk of AF (73.7% vs 56.6%, P = 0.07). Sixty‐day mortality was 2 of 38 (5.3%) in patients with AF and 4 of 83 (6.0%) in the no AF cohort (P = 1.00). The group with AF had increased length of hospitalization (13.4 days vs. 10.6 days P = 0.02). No significant differences in rates of pneumonia (31.6% vs. 21.7% P = 0.24), stricture (13.2% vs. 26.5% P = 0.10), or leak requiring return to operating room (13.2% vs. 8.4% P = 0.51) were noted between groups. We did not find an increased rate of AF in our MIE cohort compared with prior reported rates in open esophagectomy populations. AF did result in an increased length of stay but was not a predictor of other short‐term morbidities including anastomotic leak, pulmonary complications, stenosis, or 60‐day mortality.     

A Review of Adsorbents for Heavy Metal Decontamination: Growing Approach to Wastewater Treatment

Heavy metal is released from many industries into water. Before the industrial wastewater is discharged, the contamination level should be reduced to meet the recommended level as prescribed by the local laws of a country. They may be poisonous or cancerous in origin. Their presence does not only damage people, but also animals and vegetation because of their mobility, toxicity, and non-biodegradability into aquatic ecosystems. The review comprehensively discusses the progress made by various adsorbents such as natural materials, synthetic, agricultural, biopolymers, and commercial for extraction of the metal ions such as Ni²⁺, Cu²⁺, Pb²⁺, Cd²⁺, As²⁺ and Zn²⁺ along with their adsorption mechanisms. The adsorption isotherm indicates the relation between the amount adsorbed by the adsorbent and the concentration. The Freundlich isotherm explains the effective physical adsorption of the solute particle from the solution on the adsorbent and Langmuir isotherm gives an idea about the effect of various factors on the adsorption process. The adsorption kinetics data provide valuable insights into the reaction pathways, the mechanism of the sorption reaction, and solute uptake. The pseudo-first-order and pseudo-second-order models were applied to describe the sorption kinetics. The presented information can be used for the development of bio-based water treatment strategies.     

Pleural “drop metastases” 21 years after resection of a thymoma

Introduction: We describe an unusual case of pleural drop metastases 21 years after complete resection of an encapsulated thymoma in a Southeast Asian patient with myasthenia gravis (MG). Methods: This investigation includes a case report and brief review of the literature. Results: The patient presented in 2015 with generalized weakness, fatigue, and shortness of breath, but no diplopia, ptosis, dysphagia, or dysarthria. Because these symptoms were atypical for an MG exacerbation, a de‐novo work‐up was performed. Chest computed tomography (CT) showed numerous pleural nodules (“drop metastases”), and CT‐guided biopsy revealed metastatic thymoma. Conclusions: The average disease‐free interval for thymoma ranges from 68 to 86 months. Pleural and mediastinal recurrence are more common than distant hematogenous recurrence. Adverse prognostic factors include an initial higher Masaoka stage, incomplete resection, older age, and pleural or pericardial involvement. Despite apparent complete resection of thymoma, clinicians should remain vigilant for recurrence for as long as 20 years after initial management. Long‐term follow‐up with radiologic surveillance is recommended. Muscle Nerve 56 : 171–175, 2017