Neuroprotective Effects of gH625-lipoPACAP in an In Vitro Fluid Dynamic Model of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is an aggressive and devastating age-related disorder. Although the causes are still unclear, several factors, including genetic and environmental, are involved. Except for symptomatic drugs, there are not, to date, any real cures for PD. For this purpose, it is necessary develop a model to better study this disease. Neuroblastoma cell line, SH-SY5Y, differentiated with retinoic acid represents a good in vitro model to explore PD, since it maintains growth cells to differentiated neurons. In the present study, SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin that induces Parkinsonism, and the neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP), delivered by functionalized liposomes in a blood–brain barrier fluid dynamic model, were evaluated. We demonstrated PACAP neuroprotective effects when delivered by gH625-liposome on MPP+-damaged SH-SY5Y spheroids.

Hydrophobicity: The door to drug delivery

“…In HeLa cells, the absorption of Mitoxantrone by liposomes coated with gH625 and containing Mitoxantrone was enhanced, and the internalization of Mitoxantrone was increased and accelerated 122 . Furthermore, gH625 was demonstrated both in vitro and in vivo, to be able to cross the BBB and carry a variety of cargoes, which extends the possibility of applications to pathologies associated with the central nervous system 67,68,121,126 …”

“…Interestingly, not only these peptides could pass through the plasma membrane on their own, but they could favor the cellular uptake of any cargo attached to them. 67,68 Initial characterization of the uptake mechanism pointed that the uptake occurred rapidly in a receptorindependent fashion and that, in contrast to traditional based techniques, the transduction was not influenced by cell type and was efficient into nearly all cells both in vitro and in vivo with no apparent toxicity. Viral transduction presents limited capacity to be used in non-dividing cells, 69 and the application of CPPs as drug delivery enhancers has several benefits compared to viral transgene delivery.…”

“…122 Furthermore, gH625 was demonstrated both in vitro and in vivo, to be able to cross the BBB and carry a variety of cargoes, which extends the possibility of applications to pathologies associated with the central nervous system. 67,68,121,126 . These studies highlight CPP gH625 benefits for drug delivery in cancer therapy.…”

“…Currently, peptides, which were once considered too hydrophilic to pass through biological membranes, are widely employed as vehicles to aid in the intracellular delivery of non‐permeable molecules of various kinds. Interestingly, not only these peptides could pass through the plasma membrane on their own, but they could favor the cellular uptake of any cargo attached to them 67,68 . Initial characterization of the uptake mechanism pointed that the uptake occurred rapidly in a receptor‐independent fashion and that, in contrast to traditional based techniques, the transduction was not influenced by cell type and was efficient into nearly all cells both in vitro and in vivo with no apparent toxicity.…”