title: Overcoming glucocorticoid resistances and improving antitumor therapies: lipid and polymers carriers.
abstract: OBJECTIVE
  To improve chemotherapy protocols of lymphoid malignancies, by using polymeric and lipid microparticles as controlled delivery systems of dexamethasone, part of all combined chemotherapy protocols for its strong-inducing effect on malignant lymphoblasts.
  
  
  METHODS
  Polymeric microparticles were prepared by the oil-in-water-emulsion cosolvent evaporation method, andlipid microparticles by spray drying. Their cytotoxic effects on GC-sensitive PC12 cells and GC-resistant PC3 cells were characterized by cell proliferation and apoptosis assays.
  
  
  RESULTS
  Both elaboration methods rendered optimal-sized microparticles for parenteral administration with high drug loading. In vitro assays showed sustained dexamethasone release from polymeric microparticles over a month, whereas 100% dexamethasone release from lipid microparticles was achieved within 24 h. Similar PC12 cell death to that obtained with dexamethasone solution administered every 48 h was achieved with dexamethasone polymeric microparticles in 26-days assays. Dexamethasone solution and loaded polymeric microparticles induced apoptosis around 15.8 and 19.9%, respectively, after 2 days of incubation. Lipid microparticles increased further apoptosis induction in PC12 cells and, unlike dexamethasone solution and polymeric microparticles, showed antiproliferative effects on PC3 cells.
  
  
  CONCLUSIONS
  Dexamethasone polymeric microparticles constitute an alternative to current dexamethasone administration systems in combined chemotherapy, whereas dexamethasone lipid microparticles represent a potential tool to revert glucocorticoid resistance.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martín-Sabroso
authors.forename: A J
authors.initials: AJ
authors.lastname: Moreno-Ortega
authors.forename: J
authors.initials: J
authors.lastname: Aparicio-Blanco
authors.forename: A I
authors.initials: AI
authors.lastname: Fraguas-Sánchez
authors.forename: M F
authors.initials: MF
authors.lastname: Cano-Abad
authors.forename: A I
authors.initials: AI
authors.lastname: Torres-Suárez
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D016716:PC12 Cells; D010316:Particle Size; D010673:Pheochromocytoma / Q000473:pathology*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D011108:Polymers; D003907:Dexamethasone