Aj. Millest et al., SUSTAINED-RELEASE OF SALMON-CALCITONIN INVIVO FROM LACTIDE - GLYCOLIDE COPOLYMER DEPOTS, Calcified tissue international, 52(5), 1993, pp. 361-364
Studies were carried out to determine whether monolithic depot formula
tions, prepared using lactide:glycolide copolymers, could be used to a
dminister salmon calcitonin (sCT) to rats in vivo. Formulations contai
ning 2, 5, or 10% (w/w) sCT were administered subcutaneously to female
Wistar strain rats. Release of sCT was determined by measurement of p
eptide in plasma using a specific radioimmunoassay and by measurement
of residual sCT in the depots after recovery at postmortem. Plasma cal
cium concentrations and cumulative weight gain of the animals were use
d to measure pharmacological effects of the released sCT. Release of s
CT from the depots was controlled by the copolymer and was sustained f
or 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 o
f the formulations was shown to modify sCT release. Maximal release of
sCT from depots containing 10% peptide occurred over a 7 to 14-day pe
riod postadministration, with 5% sCT release occurred between days 11
and 14, and with 2% sCT, the period of maximal release was between day
s 11 and 18. Release of peptide from the depots was essentially comple
te by 21 days postadministration irrespective of the peptide loading.
These data suggest that lactide:glycolide copolymer depots may have ap
plication for the convenient clinical administration of sCT in metabol
ic bone diseases.