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Data-driven modeling of the cellular pharmacokinetics of degradable chitosan-ba...

Summers, HD; Gomes, CP; Varela-Moreira, A; Spencer, AP; Gomez-Lazaro, M; Pêgo, AP; Rees, P

Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale pro-cesses. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between controlling processes. We demonstrate data simulation techni...


A high-throughput bioimaging study to assess the impact of chitosan-based nanop...

Gomes, C; Varela-Moreira, A; Leiro, V; Lopes, C; Moreno, PM; Gomez-Lazaro, M; Pêgo, AP

By using imaging flow cytometry as a powerful statistical high-throughput technique we investigated the impact of degradation on the biological performance of trimethyl chitosan (TMC)-based nanoparticles (NPs). In order to achieve high transfection efficiencies, a precise balance between NP stability and degradation must occur. We altered the biodegradation rate of the TMC NPs by varying the degree of acetylati...


Delivery of Splice Switching Oligonucleotides by Amphiphilic Chitosan-Based Nan...

Moreno, PM; Santos, J; Gomes, C; Varela-Moreira, A; Costa, A; Leiro, V; Mansur, H; Pêgo, AP

Splice switching oligonucleotides (SSOs) are a class of single-stranded antisense oligonucleotides (ssONs) being used as gene therapeutics and demonstrating great therapeutic potential. The availability of biodegradable and biocompatible delivery vectors that could improve delivery efficiencies, reduce dosage, and, in parallel, reduce toxicity concerns could be advantageous for clinical translation. In this wor...


Translating chitosan to clinical delivery of nucleic acid-based drugs

Gomes, CP; Lopes, CD; Moreno, PM; Varela-Moreira, A; Alonso, MJ; Pêgo, AP

A number of systems based on synthetic molecules, among them cationic liposomes and poly(ethylene imine)-based polymers, have been proposed as delivery vehicles for nucleic acids. Some of these systems have even reached the market, ensuring efficient and transient transfection levels in a variety of cell types. However, toxicity issues have limited their application in vivo. In this context, chitosan, a biocomp...


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