Resumen de Cell-penetrating peptides as drug shuttles for pain management and other therapeutic applications
This thesis focuses on one of the major challenges in the drug discovery field, namely the efficient targeted delivery of therapeutic compounds with poor or nil cellular uptakes. In this regard, the thesis contributes convincing results on how cell-penetrating peptides (CPPs), acting as drug delivery vectors, can overcome pharmacokinetic issues and poor access to difficult targets, such as the central nervous system (CNS).
Specifically, and as the main achievement of the thesis, we have designed and developed an optimized, orally active, CPP-enabled peptide disruptor of the heterodimer between cannabinoid CB1 and serotonin 5HT2A receptors, thereby making way for the medical use of cannabinoids to fight pain while avoiding side effects such as memory impairment.
Similarly, we have successfully perturbed adenosine A2A receptor homodimerization by coupling an interfering peptide to a modified cyclic CPP, in yet another promising strategy for CNS disorder treatment.
As a further example of CPP-enabled delivery of poorly absorbed therapeutic molecules, we have managed to considerably increase cellular uptake into Leishmania cells of paromomycin, an anti-parasitic drug.
Altogether, this work reinforces CPP relevance as drug carriers and provides valuable insights into their design, structural optimization, coupling strategies and therapeutic validation.
