Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs.
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http://dx.doi.org/10.1038/srep33791 | DOI Listing |
AAPS PharmSciTech
January 2025
Department of Pharmaceutics, School of Pharmaceutical Science, Siksha 'O' Anusandhan University, Bhubaneswar, 751003, Odisha, India.
Transdermal drug delivery (TDD) represents a transformative paradigm in drug administration, offering advantages such as controlled drug release, enhanced patient adherence, and circumvention of hepatic first-pass metabolism. Despite these benefits, the inherent barrier function of the skin, primarily attributed to the stratum corneum, remains a significant impediment to the efficient permeation of therapeutic agents. Recent advancements have focused on macromolecular-assisted permeation enhancers, including carbohydrates, lipids, amino acids, nucleic acids, and cell-penetrating peptides, which modulate skin permeability by transiently altering its structural integrity.
View Article and Find Full Text PDFInt J Pharm
January 2025
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan; Innovative Research Center for Drug Delivery System, Institute of Biomedical Sciences, Tokushima University, 770-8505 Tokushima, Japan. Electronic address:
B cell-based vaccines are expected to provide an alternative to DC-based vaccines. However, the efficacy of antigen uptake by B cells in vitro is relatively low, and efficient antigen-loading methods must be established before B cell-based vaccines are viable in clinical settings. We recently developed an in vitro system that efficiently loads antigens into isolated splenic B cells via liposomes decorated with hydroxyl PEG (HO-PEG-Lips).
View Article and Find Full Text PDFBiointerphases
January 2025
Department of Pharmaceutical Sciences, State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning 116081, China.
The special structure of eyes and the existence of various physiological barriers make ocular drug delivery one of the most difficult problems in the pharmaceutical field. Considering the problems of patient compliance, local administration remains the preferred method of drug administration in the anterior part of eyes. However, local administration suffers from poor bioavailability, need for frequent administration, and systemic toxicity.
View Article and Find Full Text PDFBackground: The key advantage of active immunization is the induction of sustained, polyclonal antibody responses that are readily boosted by occasional immunizations. Recent clinical trial outcomes for monoclonal antibodies lecanemab and donanemab, establish the relevance of targeting pathological Abeta for clearing amyloid plaques in Alzheimer's disease. ACI-24.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The goal of the TREAT-AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Genome-wide association studies, whole genome sequencing, and gene-expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function.
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