Hypoxic-ischemic encephalopathy (HIE), initiated by the interruption of oxygenated blood supply to the brain, is a leading cause of death and lifelong disability in newborns. The pathogenesis of HIE involves a complex interplay of excitotoxicity, inflammation, and oxidative stress that results in acute to long term brain damage and functional impairments. Therapeutic hypothermia is the only approved treatment for HIE but has limited effectiveness for moderate to severe brain damage; thus, pharmacological intervention is explored as an adjunct therapy to hypothermia to further promote recovery. However, the limited bioavailability and the side-effects of systemic administration are factors that hinder the use of the candidate pharmacological agents. To overcome these barriers, therapeutic molecules may be packaged into nanoscale constructs to enable their delivery. Yet, the application of nanotechnology in infants is not well examined, and the neonatal brain presents unique challenges. Novel drug delivery platforms have the potential to magnify therapeutic effects in the damaged brain, mitigate side-effects associated with high systemic doses, and evade mechanisms that remove the drugs from circulation. Encouraging pre-clinical data demonstrates an attenuation of brain damage and increased structural and functional recovery. This review surveys the current progress in drug delivery for treating neonatal brain injury. (Journal of Controlled Release., Volume 330, 10 February 2021, Pages 765-787.)
Month: February 2021
Targeting the Brain Lesions Using Peptides: A Review Focused on the Possibility of Targeted Drug Delivery to Multiple Sclerosis Lesions
As described by Jean Martin Charcot in 1868, multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) which leads to permanent disability in patients. Following CNS insults, astrocytes and microglial cells undergo changes, which lead to scar formation in the site of injury. Owning to the pathophysiology of MS lesions, changes in both cellular and extracellular matrix (ECM) components occur over the progression of disease. In spite of advances in therapeutic approaches, drug delivery to MS lesions appears of great interest with big challenges and limitations. Targeting with peptides is a novel promising approach in the field of drug delivery. Recently peptides have been used for active targeting of different pathological disorders in which specific peptides make targeted accumulation of cargos to enhance local drug concentration at the pathological area, lead to increased therapeutic efficacy and decreased side effects. However, specific approaches for targeting the lesion in MS are still lacking. In this review, we discuss the changes of the ECM components as well as the cellular characteristics of demyelinated lesions and emphasis on opportunities for peptide based targeted drug delivery to highlight the possibility of such approaches for neurodegenerative disease with specific focus on MS.
A successful drug delivery to a specific site relies on two essential factors including; efficient entrapment of the drug within the carrier and successful delivery of drug- loaded nanocarrier to the target site without opsonisation or drug release in the circulation before reaching the organ of interest. Lactoferrin (LF) is a glycoprotein belonging to the transferrin (TF) family which can bind to TF receptors (TFRs) and LF membrane internalization receptors (LFRs) highly expressed on the cell surface of both highly proliferating cancer cells and blood brain barrier (BBB), which in turn can facilitate its accessibility to the cell nucleus. This merit could be exploited to develop actively targeted drug delivery systems that can easily cross the BBB or internalize into tumor cells. In this review, the most recent advances of utilizing LF as an active targeting ligand for different types of nanocarriers including: inorganic nanoparticles, dendrimers, synthetic biodegradable polymers, lipid nanocarriers, natural polymers, and nanoemulstions will be highlighted. Collectively, LF seems to be a promising targeting ligand in the field of nanomedicine. (International Journal of Biological Macromolecules., Volume 167, 15 January 2021, Pages 1527-1543.)