title: PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier.
abstract: Neurodegenerative diseases have an increased prevalence and incidence nowadays, mainly due to aging of the population. In addition, current treatments lack efficacy, mostly due to the presence of the blood-brain barrier (BBB) that limits the penetration of the drugs to the central nervous system. Therefore, novel drug delivery systems are required. Polymeric nanoparticles have been reported to be appropriate for this purpose. Specifically, the use of poly-(lactic-co-glycolic acid) (PLGA) seems to be advantageous due to its biocompatibility and biodegradability that ensure safe therapies. In this work, a novel approximation to develop loperamide-loaded nanoparticles is presented: their preparation by nano-emulsion templating using a low-energy method (the phase inversion composition, PIC, method). This nano-emulsification approach is a simple and very versatile technology, which allows a precise size control and it can be performed at mild process conditions. Drug-loaded PLGA nanoparticles were obtained using safe components by solvent evaporation of template nano-emulsions. Characterization of PLGA nanoparticles was performed, together with the study of the BBB crossing. The in vivo results of measuring the analgesic effect using the hot-plate test evidenced that the designed PLGA loperamide-loaded nanoparticles are able to efficiently cross the BBB, with high crossing efficiencies when their surface is functionalized with an active targeting moiety (a monoclonal antibody against the transferrin receptor). These results, together with the nanoparticle characterization performed here are expected to provide sufficient evidences to end up to clinical trials in the near future.
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C/Jordi Girona, 18-26 Barcelona, Spain; CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. Electronic address: cristina.fornaguera@iqac.csic.es.
authors.forename: C
authors.initials: C
authors.lastname: Fornaguera
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C/Jordi Girona, 18-26 Barcelona, Spain; CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Dols-Perez
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C/Jordi Girona, 18-26 Barcelona, Spain; CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Calderó
authors.affiliation: CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain; Department of Pharmacy and Pharmaceutical Technology, University of Barcelona, Av/ Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Celma
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, Av/ Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), C/Jordi Girona, 18-26 Barcelona, Spain; CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Solans
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Active targeting; Blood–brain barrier; Loperamide; Nano-emulsions; Polymeric nanoparticles