Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist: part II. In vivo performance

Autor: Hans Lindner, Pierre Broqua, Jean-Pierre Giliberto, Nathalie Oudry, Grégoire Schwach, Robert Gurny, Martin Lück
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Male
medicine.medical_specialty
medicine.drug_class
Polymers
Gonadotropin-Releasing Hormone/antagonists & inhibitors/metabolism
Pharmaceutical Science
Microextrusion
Peptide
Pharmacology
Gonadotropin-releasing hormone antagonist
Microsphere
Gonadotropin-Releasing Hormone
Rats
Sprague-Dawley
chemistry.chemical_compound
Hormone Antagonists
Polylactic Acid-Polyglycolic Acid Copolymer
Delayed-Action Preparations/administration & dosage/metabolism
In vivo
Internal medicine
medicine
Animals
Degarelix
Lactic Acid
Lactic Acid/administration & dosage/metabolism
Polymers/administration & dosage/metabolism
chemistry.chemical_classification
Luteinizing Hormone/antagonists & inhibitors/metabolism
ddc:618
ddc:617
General Medicine
Luteinizing Hormone
Controlled release
Polyglycolic Acid/administration & dosage/metabolism
Microspheres
Rats
Endocrinology
chemistry
Delayed-Action Preparations
Luteinizing hormone
Polyglycolic Acid
Biotechnology
Hormone Antagonists/administration & dosage/metabolism
Zdroj: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 57, No 3 (2004) pp. 441-6
ISSN: 0939-6411
Popis: Poly (DL-lactide-co-glycolide) microparticles (MP) containing a highly potent peptidic gonadotropin releasing hormone antagonist (degarelix) of interest in the prostate cancer indication were screened for biological performance. Efficacy was tested in a castrated male rat model at 3 doses (0.4, 1.0 and 1.5 mg/kg) and assessed as inhibition of luteinizing hormone (LH) secretion. When increasing the dose, onset of inhibition was faster, inhibition was more intense, and duration of action was prolonged. The MP type was also highly influent. If spray-dried and microextrusion particles exhibited comparable potencies, double emulsion microspheres were significantly less potent, both for onset and duration of inhibition. Interestingly, for the latter type it was found that the degarelix fraction released upon reconstitution in the solution for injection was significantly lower (max 0.3%), in comparison to spray-dried MP (max 2%) or microextrusion (max 4%). With the three types of particles, increasing peptide content was detrimental for duration of action, but only little difference was noticed between particles based on different polymers. At 1.5 mg/kg, LH inhibition was achieved over 36 days with spray-dried MP based on 75/25 lactate/glycolate copolymer. This was superior by 1 week to the performance of unformulated degarelix given at the same dose.
Databáze: OpenAIRE
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