title: Brain targeted delivery of carmustine using solid lipid nanoparticles modified with tamoxifen and lactoferrin for antitumor proliferation.
abstract: Solid lipid nanoparticles (SLNs) conjugated with tamoxifen (TX) and lactoferrin (Lf) were applied to carry anticancer carmustine (BCNU) across the blood-brain barrier (BBB) for enhanced antiproliferation against glioblastoma multiforme (GBM). BCNU-loaded SLNs with modified TX and Lf (TX-Lf-BCNU-SLNs) were used to penetrate a monolayer of human brain-microvascular endothelial cells (HBMECs) and human astrocytes and to target malignant U87MG cells. The surface TX and Lf on TX-Lf-BCNU-SLNs improved the characteristics of sustained release for BCNU. When compared with BCNU-loaded SLNs, TX-Lf-BCNU-SLNs increased the BBB permeability coefficient for BCNU about ten times. In addition, TX-BCNU-SLNs considerably promoted the fluorescent intensity of intracellular acetomethoxy derivative of calcein (calcein-AM) in HBMECs via endocytosis. However, the conjugated Lf could only slightly increase the fluorescence of calcein-AM. Moreover, the order of formulation in the inhibition to U87MG cells was TX-Lf-BCNU-SLNs>TX-BCNU-SLNs>Lf-BCNU-SLNs>BCNU-SLNs. TX-Lf-BCNU-SLNs can be effective in infiltrating the BBB and delivering BCNU to GBM for future chemotherapy application.
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. Electronic address: chmyck@ccu.edu.tw.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China.
authors.forename: Shih-Jue
authors.initials: SJ
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002330:Carmustine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005452:Fluoresceins / Q000737:chemistry; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles; D010539:Permeability; D013629:Tamoxifen / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005452:Fluoresceins; D008055:Lipids; D013629:Tamoxifen; C085925:calcein AM; D007781:Lactoferrin; D002330:Carmustine
keywords: Blood–brain barrier; Carmustine; Glioblastoma multiforme; Lactoferrin; Solid lipid nanoparticle; Tamoxifen