Repositioning of drugs for Parkinson's disease and pharmaceutical nanotechnology tools for their optimization

Abstract

Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science, and Scopus from January 2015 at the end of 2021, with the descriptors "Parkinson's disease" and "drug repositioning" or "drug repurposing". We identified 28 drugs as potential candidates, and six of them were found in repositioning clinical trials for PD. However, a limitation of many of these drugs to achieve therapeutic success is their inability to cross the blood-brain barrier (BBB), as is the case with nilotinib, which has shown promising outcomes in clinical trials. We suggest reformulating these drugs in biodegradable nanoparticles (NPs) based on lipids and polymers to perform future trials. As a complementary strategy, we propose functionalizing the NPs surface by adding materials to the surface layer. Among other advantages, functionalization can promote efficient crossing through the BBB and improve the affinity of NPs towards certain brain regions. The main parameters to consider for the design of NPs targeting the central nervous system are highlighted, such as size, PDI, morphology, drug load, and Z potential. Finally, current advances in the use of NPs for Parkinson's disease are cited.

Keywords: Drug repositioning; Drug repurposing; Nanocarriers; Nanoparticles; Parkinson’s disease; Pharmaceutical nanotechnology.

Fig. 1

Drug repositioning and polypharmacology. A drug can have more than one active site, which allows the molecule to target different organs and gives rise to multiple therapeutic indications; this is known as polypharmacology and is used in the repositioning of drugs since there are drugs approved for a therapeutic indication for which its biological target is known, but with the potential to target other tissues and alleviate other pathologies

Fig. 2

The number of publications indexed in PubMed, Web of Science, and Scopus that contain the terms “(Parkinson’s disease) and (drug repositioning or drug repurposing)” in the last years (01/2015–07/2021)

Fig. 3

Biodegradable nanoparticles. Nanosystems are proposed for the optimization of drug delivery in PD. NPs based on lipids and polymers are the most interesting since they are synthesized based on biodegradable and biocompatible materials representing low toxicity and a high capacity to modify their physicochemical properties

Fig. 4

a Increased specificity towards BBB. The surface coating of NPs with suitable materials can increase the specificity towards the BBB; these materials (as mentioned in Table 2) can be polymers, proteins, antibodies, peptides, and other additives. b Receptor-mediated transcytosis. The passage through the BBB is exemplified through receptor-mediated transcytosis. A very frequently used pathway for the transport of NPs to the brain, for this use, is assembled with specific receptors found in the BBB