title: Retinal ganglion cells survival in a glaucoma model by GDNF/Vit E PLGA microspheres prepared according to a novel microencapsulation procedure.
abstract: The present experimental work describes the use of a novel protein encapsulation method to achieve protection of the biological factor during the microencapsulation procedure. With this aim, the protein is included in poly(lactic-co-glycolic acid) (PLGA) microspheres without any preliminary manipulation, in contrast to the traditional S/O/W (solid-in-oil-in-water) method where the bioactive substance is first dissolved and then freeze-dried in the presence of lyoprotectors. Furthermore, the presented technique involves the use of an oily additive, vitamin E (Vit E), useful from a technological point of view, by promoting additional protein protection and also from a pharmacological point of view, because of its antioxidant and antiproliferative properties. Application of this microencapsulation technique has been performed for GDNF (glial cell line-derived neurotrophic factor) designed for the treatment of optic nerve degenerative diseases, such as glaucoma, the second leading cause of blindness in the western world. The protein was released in vitro in its bioactive form for more than three months, demonstrated by the survival of their potential target cells (photoreceptors and retinal ganglion cells (RGC)). Moreover, the intravitreal injection of GDNF/Vit E PLGA microspheres in an experimental animal model of glaucoma significantly increased RGC survival compared with GDNF, Vit E or blank microspheres (p<0.01). This effect was present for at least eleven weeks, which suggests that the formulation prepared may be clinically useful as a neuroprotective tool in the treatment of glaucomatous optic neuropathy.
authors.affiliation: Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Avda. Complutense s/n, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Checa-Casalengua
authors.forename: Caihui
authors.initials: C
authors.lastname: Jiang
authors.forename: Irene
authors.initials: I
authors.lastname: Bravo-Osuna
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.forename: Irene T
authors.initials: IT
authors.lastname: Molina-Martínez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Young
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero-Vanrell
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D007429:Intraocular Pressure / Q000187:drug effects; D058449:Intravitreal Injections; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013499:Surface Properties; D014810:Vitamin E / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D004337:Drug Carriers; D004338:Drug Combinations; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid