Coupling the in vivo performance to the in vitro characterization of PLGA microparticles.
Coupling the in vivo performance to the in vitro characterization of PLGA microparticles.
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DOI：
10.1016/j.ijpharm.2021.120738
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发表时间：
2021-07-15
影响因子：
5.8
通讯作者：
Park, Kinam
中科院分区：
文献类型：
--
作者：
Otte, Andrew;Damen, Frederick;Goergen, Craig;Park, Kinam
本研究的主要目的是确定啮齿动物饲养条件（特别是饲养气候）是否会通过改变皮下空间的温度影响聚（丙交酯-共-乙交酯）（PLGA）微球的体内性能。Vivitrol®，一种每月一次的纳洛酮可注射悬浮液，被选为本研究的模型PLGA微粒制剂。使用两批Vivitrol确定批次之间可能存在的任何潜在差异，以及体外表征技术是否可以描述任何变化。纳洛酮-PLGA微粒的药代动力学在啮齿动物模型中在两种不同的圈养气候（20与25 °C）下测定。结果表明，外壳温度的这种差异导致皮下温度的变化，但实际上在窄范围（36.31-36.77 °C）内，因此对皮下注射的微粒的体内性能的影响最小。摇瓶法用于表征在35、36和37 °C下的体外释放，并证明在该温度范围内体外释放曲线存在显著差异。发现两个批次的体外表征差异很小，虽然这些结果没有提供统计学意义，但局部体内温度可能是评价微粒性能时应考虑的参数。IVIVC证明在37 °C下的体外释放可能不能准确地代表体内条件（即，在某些情况下，较低的体外释放温度可以更准确地代表体内微环境并提供更好的相关性。未来的研究将基于在35-37 °C范围内的体外释放曲线中观察到的显著差异，确定温度和特别是共容纳可能对可注射聚合物微粒的体内性能的相对影响的程度。
The main objective of the study was to determine if rodent housing conditions, specifically housing climate, could impact the in vivo performance of poly(lactide-co-glycolide) (PLGA) microspheres through temperature modification of the subcutaneous space. Vivitrol®, a once monthly naltrexone injectable suspension, was chosen as a model PLGA microparticle formulation for this study. Two lots of Vivitrol were used to ascertain any potential differences that may exist between the batches and if in vitro characterization techniques could delineate any variation(s). The pharmacokinetics of the naltrexone-PLGA microparticles were determined in the rodent model under two different housing climates (20 vs. 25 °C). The results demonstrate that such difference in housing temperature resulted in a change in subcutaneous temperature but actually within a narrow range (36.31–36.77 °C) and thus minimally influenced the in vivo performance of subcutaneously injected microparticles. The shake-flask method was used to characterize the in vitro release at 35, 36, and 37 °C and demonstrated significant differences in the in vitro release profiles across this range of temperatures. Minimal differences in the in vitro characterization of the two lots were found. While these results did not provide statistical significance, the local in vivo temperature may be a parameter that should be considered when evaluating microparticle performance. The IVIVCs demonstrate that in vitro release at 37 °C may not accurately represent the in vivo conditions (i.e., subcutaneous space in rodents), and in certain instances lower in vitro release temperatures may more accurately represent the in vivo microenvironment and provide better correlations. Future studies will determine the extent temperature and specifically co-housing, may have on the relative impact of the in vivo performance of injectable polymeric microparticles based upon the significant differences observed in the in vitro release profiles across the range of 35–37 °C.
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