Add time:08/18/2019         Source:sciencedirect.com

Growth hormone releasing factor (GRF) stimulates pituitary somatotropin (ST) release. Somatotropin directly or indirectly through insulin like-growth factor I decreases lipogenesis and promotes protein accretion resulting in enhanced growth in food producing animals such as cattle and swine. A sustained release formulation is required to capitalize on GRF biological properties since frequent animal handling in a production facility is difficult. Sustained durations were evaluated with aqueous, oil and microsphere suspensions containing a previously discovered metabolic stable growth hormone releasing factor analog (Ile2,Ser8,28,Ala15,Leu27,Hse30bGRF(1-30)-NH-ethyl). Serum ST concentrations were measured periodically during a 35-day period after the formulations were administered to meal-fed Holstein steers. Areas under the ST daily curves (ST-AUC) formed the basis for determining the time daily ST-AUC returned to baseline for each treatment group. Time to return to baseline was 21 days when delivering subcutaneously a 200 or 400 mg dose of a 20% oil suspension and 14 days for a 200 mg dose at 10% load in poly(lactide-co-glycolide) microspheres. The longest duration, 35 days, was achieved with a 200 mg dose of an 18% aqueous nanosuspension. A zero-order release was observed with the 18% aqueous formulation as indicated by the ST-AUC not changing from days 7 through 35. Formation of fibrils and subsequent dissolution from the fibrils was thought important in sustaining the drug release.

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