title: Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters.
abstract: Poly(lactide-co-glycolide) (PLGA) nanoparticles coated with poloxamer 188 (Pluronic((R)) F-68) or polysorbate 80 (Tween((R)) 80) enable an efficient brain delivery of the drugs after intravenous injection. This ability was evidenced by two different pharmacological test systems employing as model drugs the anti-tumour antibiotic doxorubicin and the agonist of opioid receptors loperamide, which being P-gp substrates can cross the blood-brain barrier (BBB) only in pharmacologically insignificant amounts: binding of doxorubicin to the surfactant-coated PLGA nanoparticles, however, enabled a high anti-tumour effect against an intracranial 101/8 glioblastoma in rats, and the penetration of nanoparticle-bound loperamide into the brain was demonstrated by the induction of central analgesic effects in mice. Both pharmacological tests could demonstrate that therapeutic amounts of the drugs were delivered to the sites of action in the brain and showed the high efficiency of the surfactant-coated PLGA nanoparticles for brain delivery. The results of the study also demonstrated that the efficacy of brain delivery by nanoparticles not only is influenced by the coating surfactants but also by other formulation parameters such as core polymer, drug, and stabilizer.
authors.affiliation: Nanosystem Ltd., Moscow, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gelperina
authors.forename: Olga
authors.initials: O
authors.lastname: Maksimenko
authors.forename: Alexander
authors.initials: A
authors.lastname: Khalansky
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Vanchugova
authors.forename: Elena
authors.initials: E
authors.lastname: Shipulo
authors.forename: Kenul
authors.initials: K
authors.lastname: Abbasova
authors.forename: Rustam
authors.initials: R
authors.lastname: Berdiev
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wohlfart
authors.forename: Nina
authors.initials: N
authors.lastname: Chepurnova
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D008139:Loperamide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017288:Pain Threshold / Q000187:drug effects*; D020442:Poloxamer / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry / Q000494:pharmacology*; D011136:Polysorbates / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D011136:Polysorbates; D013501:Surface-Active Agents; D020442:Poloxamer; D011098:Polyglactin 910; D008139:Loperamide; D004317:Doxorubicin