Barra Teresa, Falanga Annarita, Bellavita Rosa, Laforgia Vincenza, Prisco Marina, Galdiero Stefania, Valiante Salvatore
Deparment of Biology, University of Naples Federico II, Naples, Italy.
Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy.
Front Physiol. 2022 Aug 19;13:932099. doi: 10.3389/fphys.2022.932099. eCollection 2022.
The blood-brain barrier (BBB) selectively protects the central nervous system (CNS) from external insults, but its function can represent a limit for the passage of therapeutic molecules. Numerous models of the BBB have been realized in order to study the passage of drugs for neurodegenerative diseases, but these models are not very representative of the physiological conditions because of a limited supply of oxygen and nutrients due to static conditions. To avoid this phenomenon, we used a millifluidic bioreactor model that ensures a circulation of the medium and, therefore, of the nutrients, thanks to the continuous laminar flow. This dynamic model consists of a double-culture chamber separated by a membrane on which brain endothelial cells are cultured in order to evaluate the passage of the drug. Furthermore, in the lower chamber, SH-SY5Y were seeded as 3D spheroids to evaluate the drug passage through these cells. As nanodelivery system, we used liposomes functionalized with viral fusion peptide to evaluate the passage of a neuroprotective agent, pituitary adenylate cyclase-activating polypeptide (PACAP), through the dynamic model of the BBB. We showed that our nanodelivery system, made of functionalized liposomes and loaded with specific molecules, efficiently crosses the fluid-dynamic model of the BBB. Our findings represent an important step for further experimental investigations on PACAP administration as a therapeutic agent by an enhanced drug delivery system. Our results can improve the diffusion of good practice in neuroscience laboratories, helping to spread the 3R rules.
血脑屏障（BBB）选择性地保护中枢神经系统（CNS）免受外部侵害，但其功能可能成为治疗分子通过的限制因素。为了研究治疗神经退行性疾病药物的通过情况，已经建立了许多血脑屏障模型，但由于静态条件下氧气和营养物质供应有限，这些模型不能很好地代表生理状况。为避免这种现象，我们使用了一种微流控生物反应器模型，由于连续层流，该模型可确保培养基以及营养物质的循环。这个动态模型由一个双培养室组成，中间由一层膜隔开，在膜上培养脑内皮细胞以评估药物的通过情况。此外，在下室中，将SH-SY5Y接种为三维球体，以评估药物通过这些细胞的情况。作为纳米递送系统，我们使用了用病毒融合肽功能化的脂质体，以评估神经保护剂垂体腺苷酸环化酶激活多肽（PACAP）通过血脑屏障动态模型的情况。我们表明，我们由功能化脂质体组成并装载有特定分子的纳米递送系统能够有效地穿过血脑屏障的流体动力学模型。我们的研究结果是进一步通过增强药物递送系统对PACAP作为治疗剂进行实验研究的重要一步。我们的结果可以改善神经科学实验室中良好实践的传播，有助于推广3R规则。
