Sustained release of salmon calcitonin in vivo from lactide: glycolide copolymer depots.
Studies were carried out to determine whether monolithic depot formulations, prepared using lactide:glycolide copolymers, could be used to administer salmon calcitonin (sCT) to rats in vivo. Formulations containing 2, 5, or 10% (w/w) sCT were administered subcutaneously to female Wistar strain rats. Release of sCT was determined by measurement of peptide in plasma using a specific radioimmunoassay and by measurement of residual sCT in the depots after recovery at postmortem. Plasma calcium concentrations and cumulative weight gain of the animals were used to measure pharmacological effects of the released sCT. Release of sCT from the depots was controlled by the copolymer and was sustained for periods up to 10 days. However, the release of sCT from the depots did not significantly alter plasma calcium concentrations, and effects on cumulative weight gain were small and transient. Peptide loading of the formulations was shown to modify sCT release. Maximal release of sCT from depots containing 10% peptide occurred over a 7 to 14-day period postadministration, with 5% sCT release occurred between days 11 and 14, and with 2% sCT, the period of maximal release was between days 11 and 18. Release of peptide from the depots was essentially complete by 21 days postadministration irrespective of the peptide loading. These data suggest that lactide:glycolide copolymer depots may have application for the convenient clinical administration of sCT in metabolic bone diseases.
Millest
A J
AJ
YIM Department, ZENECA Pharmaceuticals, Mereside, Alderley Park, Macclesfield, United Kingdom.
Evans
J R
JR
Young
J J
JJ
Johnstone
D
D
D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005260:Female; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects
D003692:Delayed-Action Preparations; D004343:Drug Implants; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium