Papers, explained in our own words

1. Liposomal Delivery Systems: Design Optimization and Current Applications

Liposomes are attractive pharmaceutical carriers because they encapsulate hydrophilic and hydrophobic drugs and are biocompatible and biodegradable. However, conventional liposomes suffer from aggregation/fusion, premature payload release, rapid clearance by the mononuclear phagocyte system (MPS), low entrapment efficiency for some drugs, poor target selectivity, and inefficient intracellular delivery. Design optimization is needed to improve. Remote loading achieved encapsulation efficiency up to 90%; cyclodextrin-based loading achieved drug-to-lipid ratios >1000-fold higher than passive loading. - Doxil, a PEGylated liposomal doxorubicin formulation.

2. Attachment of Cell-Binding Ligands to Arginine-Rich Cell-Penetrating Peptides Enables Cytosolic Translocation of Complexed siRNA

Skye Zeller, Chang Seon Choi, Pradeep D. Uchil, Hong-Seok Ban, Alyssa Siefert, Tarek M. Fahmy, Walther Mothes, Sang-Kyung Lee, Priti Kumar

Arginine-rich cell-penetrating peptides (CPPs) such as nona-arginine (9R) can effectively translocate covalently attached biomolecules into cells, but poorly deliver electrostatically complexed siRNA, with most CPP:siRNA complexes trapped in endosomes. The mechanism by which ligand attachment to 9R overcomes this barrier to enable functional siRNA delivery was unknown. ### Native 9R vs. Ligand-9R: siRNA Uptake | Formulation | Cell Type | Uptake (MFI, 24 h) | Gene Silencing | |-----------------|---------------|------------------------|-------------------| | 9DR:siRNA | Neuro2a | 6.7 ±.

3. Modeling the endosomal escape of cell-penetrating peptides using a transmembrane pH gradient

Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund

Cell-penetrating peptides (CPPs) can internalize cells with biologically active cargo, but endosomal entrapment is a major limitation for cytoplasmic delivery, as cargo molecules must escape the endosome before degradation and acidification. While CPPs are known to enter cells via endocytosis, the background mechanism(s) of endosomal escape remain poorly understood. A model system that mimics late endosomal pH gradients is needed to study how. ### pH Gradient Establishment (BR-LUVs) | Vesicle Composition | pH Gradient Efficiency | Comment | |-------------------------|---------------------------|-------------| | POPC/POPG (20% negative) | Strongest | Used for.

4. Uptake of cell-penetrating peptides is dependent on peptide-to-cell ratio rather than on peptide concentration

Mattias Hallbrink, Johannes Oehlke, Gisela Papsdorf, Michael Bienert

Cell-penetrating peptides (CPPs) efficiently translocate across plasma membranes and are promising delivery vectors for therapeutic macromolecules. However, the influence of cell state, density, and peptide-to-cell ratio on CPP uptake and degradation has received little attention. Understanding whether CPP uptake is governed by peptide concentration or by the peptide-to-cell ratio is critical for experimental design and reproducibility, as. ### Effect of Culture Age on MAP Uptake (1 μM, 1 h) | Culture Age | Control Cells (μM) | Energy-Depleted Cells (μM) | |-----------------|-----------------------|-------------------------------| | 2 days | 24 | 20 | | 4.