Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

译文

:Labrasol是一种基于脂质的自乳化赋形剂,用于制备旨在用于口服的亲脂性药物。它主要由具有中等酰基链的PEG酯和甘油酯组成,它们是消化脂肪酶的潜在底物。本研究研究了猪胰腺提取物,人胰液和几种纯化的消化脂肪酶对Labrasol的水解作用。古典人胰脂肪酶(HPL)和猪胰脂肪酶是参与饮食甘油三酸酯消化的主要脂肪酶,它们对整个Labrasol赋形剂以及甘油酯和PEG酯的分离部分均具有非常低的活性。另一方面,胃脂肪酶,胰脂肪酶相关蛋白2(PLRP2)和羧基酯水解酶(CEH)对拉布拉索尔表现出较高的比活性。发现这些脂肪酶水解用作单独底物的Labrasol的主要成分(PEG酯和甘油单酸酯),而发现这些酯是HPL的不良底物。因此,胰腺提取物和人胰液对Labrasol的脂解活性主要归因于CEH和PLRP2的联合作用。这两种胰酶以及胃脂肪酶可能​​是口服服用拉布拉索尔体内脂解的主要酶。

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