In Vitro and In Vivo Release of Poly(DL-Lactic Acid) Microspheres Containing Neurotensin Analogue Prepared by Novel Oil-in-Water Solvent Evaporation Method

摘要: Poly(DL-lactic acid) (PLA) microspheres containing a neurotensin analogue [NA; H(CH3)—Arg—Lys—Pro—Trp—tert-Leu-Leu—OEt · 3HCl] were prepared by novel oil-in-water (o/w) solvent evaporation method, and the release behaviors evaluated in vitro. About 20% of loaded NA was released initially, subsequent lasted for month from with PLA molecular weight 2000 (PLA 2000). A smaller initial 4000 6000 found, but lag time 2–3 weeks during which drug not observed microspheres. The addition relatively hydrophilic monoglycerides decreased time, fairly constant achieved. pharmacokinetic behavior studied rats. after subcutaneous injection exhibited pseudo-zero-order kinetics 1 month. reflected sharp increase plasma levels de-ester form [H(CH3)—Arg—Lys—Pro—Trp—tert-Leu—Leu—OH], steady-state agreed well predicted obtained analysis constant-infusion kinetics.