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Fulltext Nanoscale drug delivery systems and the blood-brain barrier

Alyautdin R, Khalin I, Nafeeza MI, Haron MH, Kuznetsov D

Int J Nanomedicine, 2014;9:795-811.
PMID: 24550672 DOI: 10.2147/IJN.S52236

The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.
Fulltext Return to flying after coronary artery disease: A case series among Malaysian pilots

Mohammad Z, Ismail R, Mohamed Rus MR, Haron MH

J Occup Health, 2021 Jan;63(1):e12241.
PMID: 34155722 DOI: 10.1002/1348-9585.12241

OBJECTIVES: Pilots with coronary artery disease (CAD) are at increased risk of myocardial infarction, stroke, and possibly death. Return to flying duties may be considered after a detailed risk assessment. The aim of this retrospective case series is to describe the return to flying duty process.
METHODS: We conducted a retrospective case review of pilots diagnosed with CAD at the Institute of Aviation Medicine (IAM), Royal Malaysian Air Force (RMAF) in October 2020.
RESULTS: Thirteen cases of CAD were included in the review. Ten pilots were diagnosed after developing acute coronary syndrome; the remaining three pilots were diagnosed during a routine medical examination via an exercise stress test. Twelve pilots required a revascularization procedure. A total of 11 pilots (84.6%) were recertified for flying duties, while another two were disqualified. The duration to recertification for these 11 pilots was between three months and one year.
CONCLUSIONS: The risk assessment was initiated with initial risk-stratification using population-appropriate risk calculator combined with the 4 × 4 aeromedical risk matrix. The reassessment of return to flying after coronary artery disease must be carried out no sooner than six months after the event. Pilots must be hemodynamically stable with no evidence of significant inducible ischemic left and a minimum 50% of ventricular ejection fraction (LVEF). A follow-up is recommended at the initial six months after recertification and then annually with a routine noninvasive cardiac assessment.
Fulltext Natural Product-based Nanomedicine: Recent Advances and Issues for the Treatment of Alzheimer's Disease

Woon CK, Hui WK, Abas R, Haron MH, Das S, Lin TS

Curr Neuropharmacol, 2022;20(8):1498-1518.
PMID: 34923947 DOI: 10.2174/1570159X20666211217163540

Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and their severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano-sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material's bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicinebased approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

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