Document Detail


Efficacy of subconjunctival cyclosporin-containing microspheres on keratoplasty rejection in the rabbit.
MedLine Citation:
PMID:  10502059     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The purpose of this study was to evaluate microspheres of PLGA containing cyclosporin (CsA) as a subconjunctival drug delivery system and to test their efficacy in the prevention of corneal allograft rejection in the rabbit. METHODS: Rabbits were injected subconjunctivally with a solution of CsA (CsA-AR) (20 animals) or a microsphere suspension of CsA (CsA-MP) (20 animals), with equivalent drug concentrations (15 mg/ml). The concentration of CsA in the aqueous, cornea and blood was measured by radioimmunoassay at different times thereafter. In other rabbits, 40 allogeneic grafts were performed. Animals were divided into four groups that received the following subconjunctival treatments: group 1: AR solution (solvents of CsA-AR solution); group 2: CsA-AR solution; group 3: MP suspension (empty microspheres); group 4: CsA-MP suspension. RESULTS: Mean corneal levels of CsA were 1174+/-830, 918+/-179, 972+/-580, 268+/-182 and 243+/-162 ng/ml at 12, 24 and 48 h and 7 and 14 days after the injection of CsA-AR. For the CsA-MP suspension, corneal concentrations were 1195+/-321, 234+/-147 and 88+/-77 ng/ml at 12, 24 and 48 h but subsequently dropped to undetectable levels. Blood and aqueous levels were undetectable. Treatment with CsA significantly improved the survival time and survival rate of grafts in the CsA-treated groups (2, 4) over grafts in non-CsA-treated groups (1, 3). There was no significant difference in the graft survival curve between groups 2 and 4. CONCLUSION: CsA-containing microspheres might be a promising formulation in the prevention of corneal graft rejection. Since the levels of CsA in blood were undetectable, this treatment might avoid the problems associated with systemic side effects.
Authors:
M V de Rojas Silva; M T Rodríguez-Ares; M Sánchez-Salorio; M J Lamas Díaz; J Cuevas Alvarez; J L Vila Jato; C Capeans Tomé
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie     Volume:  237     ISSN:  0721-832X     ISO Abbreviation:  Graefes Arch. Clin. Exp. Ophthalmol.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-17     Completed Date:  1999-11-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8205248     Medline TA:  Graefes Arch Clin Exp Ophthalmol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  840-7     Citation Subset:  IM    
Affiliation:
Instituto Galego de Oftalmoloxía, Complexo Hospitalario Universitario, Hospital Xeral de Galicia, c/ Galeras s/n, E-15705 Santiago de Compostela, Spain. ingo@corevia.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Aqueous Humor / metabolism
Biocompatible Materials*
Conjunctiva
Cornea / metabolism,  pathology
Corneal Transplantation* / pathology
Cyclosporine / administration & dosage*,  pharmacokinetics
Disease Models, Animal
Drug Delivery Systems*
Graft Rejection / metabolism,  pathology,  prevention & control*
Graft Survival
Immunosuppressive Agents / administration & dosage*,  pharmacokinetics
Injections
Lactic Acid*
Microspheres
Polyglycolic Acid*
Polymers*
Rabbits
Radioimmunoassay
Treatment Outcome
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Immunosuppressive Agents; 0/Polymers; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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