Appel B, Maschke A, Weiser B, Sarhan H, Englert C, Angele P, Blunk T, Göpferich A
Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany.
Int J Pharm. 2006 May 18;314(2):170-8. doi: 10.1016/j.ijpharm.2005.11.049. Epub 2006 Mar 29.
Controlled release systems for growth factors and morphogens are potentially powerful tools for the engineering or the treatment of living tissues. However, due to possible instabilities of the protein during manufacture, storage, and release, in the development of new release systems it is paramount to investigate into the maintenance of bioactivity of the protein. Within this study, recently developed protein releasing lipid matrix cylinders of 2 mm diameter and 2 mm height made from glycerol tripalmitate were manufactured in a compression process without further additives. Insulin in different concentrations (0.2%, 1%, and 2%) served as model protein. The bioactivity of the protein released from the matrices was investigated in a long-term cartilage engineering culture for up to four weeks; additionally, the release profiles were determined using ELISA. Insulin released from the matrices increased the wet weights of the cartilaginous cell-polymer constructs (up to 3.2-fold), the amount of GAG and collagen in the constructs (up to 2.4-fold and 3.2-fold, respectively) and the GAG and collagen content per cell (1.8-fold and 2.5-fold, respectively), compared to the control. The dose-dependent effects on tissue development correlated well with release profiles from the matrices with different insulin loading. In conclusion, the lipid matrices, preserving the bioactivity of incorporated and released protein, are suggested as a suitable carrier system for use in tissue engineering or for the localized treatment of tissues with highly potent protein drugs such as used in the therapy of brain cancer or neurodegenerative CNS diseases.
生长因子和形态发生素的控释系统对于活组织的工程构建或治疗而言，可能是强大的工具。然而，由于蛋白质在制造、储存和释放过程中可能存在不稳定性，在开发新的释放系统时，研究蛋白质生物活性的维持至关重要。在本研究中，由三棕榈酸甘油酯制成的直径2毫米、高2毫米的新型蛋白质释放脂质基质圆柱体，是在无其他添加剂的压缩过程中制造的。不同浓度（0.2%、1%和2%）的胰岛素用作模型蛋白。在长达四周的长期软骨工程培养中，研究了从基质中释放的蛋白质的生物活性；此外，使用酶联免疫吸附测定法（ELISA）测定释放曲线。与对照组相比，从基质中释放的胰岛素增加了软骨细胞 - 聚合物构建体的湿重（高达3.2倍）、构建体中糖胺聚糖（GAG）和胶原蛋白的量（分别高达2.4倍和3.2倍）以及每个细胞的GAG和胶原蛋白含量（分别为倍1.8和2.5倍）。对组织发育的剂量依赖性效应与不同胰岛素负载量的基质的释放曲线密切相关。总之，脂质基质能够保持掺入和释放的蛋白质的生物活性，被认为是一种适用于组织工程或用于用高效蛋白质药物对组织进行局部治疗的载体系统，如用于治疗脑癌或神经退行性中枢神经系统疾病。
