title: From naturally-occurring neurotoxic agents to CNS shuttles for drug delivery.
abstract: Central nervous system (CNS) diseases are hard to diagnose and therapeutically target due to the blood brain barrier (BBB), which prevents most drugs from reaching their sites of action within the CNS. Brain drug delivery systems were conceived to bypass the BBB and were derived from anatomical and functional analysis of the BBB; this analysis led researchers to take advantage of brain endothelial membrane physiology to allow drug access across the BBB. Both receptors and carriers can be used to transport endogenous and exogenous substances into the CNS. Combining a drug with substances that take advantage of these internalization mechanisms is a widely exploited strategy for drug delivery because it is an indirect method that overcomes the BBB in a non-invasive way and is therefore less dangerous and costly than invasive methods. Neurotoxins, among other naturally-occurring substances, may be used as drug carriers to specifically target the CNS. This review covers the current delivery systems that take advantage of the non-toxic components of neurotoxins to overcome the BBB and reach the CNS. We hope to give insights to researchers toward developing new delivery systems that exploit the positive features of substances usually regarded as natural hazards.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Soddu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
authors.affiliation: CESPU, - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra-PRD, Portugal; INEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy. Electronic address: eligav@uniss.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
mesh_terms: D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008954:Models, Biological; D009498:Neurotoxins / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002491:Central Nervous System Agents; D009498:Neurotoxins
keywords: Blood brain barrier; Brain delivery systems; CNS diseases; CNS shuttles; Neurotoxins