Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (beta-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the central nervous system (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood-brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. This review gives an account of the BBB and discusses the literature on biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications that can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders, such as AD. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism.
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http://dx.doi.org/10.1016/j.jconrel.2005.07.024 | DOI Listing |
Biomacromolecules
January 2025
Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Nadia, Mohanpur 741246, West Bengal, India.
The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane () with aryl boronic ester-based diol () moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza--indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both and intracellular amastigote burden compared to the free AmB.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.
Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA binding protein of Epstein-Barr virus (EBV), is essential for viral genome replication and maintenance and is therefore an attractive target for the therapeutic intervention of EBV-associated cancers. Several EBNA1-specific inhibitors have demonstrated the ability to block EBNA1 function in vitro, but practical delivery strategies for these inhibitors in vivo are still lacking. Here, we report an intelligent hierarchical targeting theranostic nanosystem (denoted as mZGOCS@MnO-P5) that integrates an azide (N3) terminal dual-targeting peptide (N3-P5), a tumor microenvironment-responsive degradable MnO nanosheet, and a mesoporous ZnGaO:Cr, Sn near-infrared persistent luminescence (NIR-PL) nanosphere (mZGOCS).
View Article and Find Full Text PDFSci Adv
January 2025
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Particle elasticity has widely been established to substantially influence immune cell clearance and circulation time of vascular-targeted carriers (VTCs). However, prior studies have primarily investigated interactions with macrophages, monocytic cell lines, and in vivo murine models. Interactions between particles and human neutrophils remain largely unexplored, although they represent a critical aspect of VTC performance.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Cardiac Surgery, Peking University Third Hospital, Beijing 100191, China.
Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China.
Leishmaniasis, a neglected tropical disease caused by Leishmania parasites, continues to pose global health challenges. Current treatments face issues like resistance, safety, efficacy, and cost. This review covers the discovery, mechanisms of action, clinical applications, and limitations of key antileishmanial agents: pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine.
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