高级星形细胞瘤中最危险的类型是胶质母细胞瘤多形性。该研究的目标是通过鼻腔递送来制备乳铁蛋白共轭替莫唑胺和白藜芦醇联合载药纳米脂质胶囊，用于胶质母细胞瘤的治疗和脑靶向。使用组合指数法确定了替莫唑胺和白藜芦醇的协同作用，选取了1：1的比例。使用质量设计方法（QbD）通过中心组合设计（CCRD）方法制备和优化纳米脂质胶囊，以最小的粒径、最大的透过率和最大的封闭率为目标。经优化的LTR-NLC具有期望的平均粒径（209.3 nm），窄的PDI，高的透过率（> 95％）和更好的封闭率（替莫唑胺为95.26％，白藜芦醇为87.59％）。通过体外渗透研究发现，LTR-NLC的渗透率达到了24小时为77.43％，替莫唑胺和白藜芦醇悬浮液的渗透率分别为25.76％和31.10％。相比药物悬浮液，纳米脂质胶囊的药物渗透增加了近3倍。LTR-NLC处理组的IC50值也显著更好。因此，根据该研究的发现，可以得出结论，LTR-NLC可能是胶质母细胞瘤治疗的有效制剂。 版权所有 © 2023 Elsevier B.V. 发表

The most dangerous type of high-grade astrocytoma is glioblastoma multiforme. The objective of the work was to engineer lactoferrin conjugated temozolomide and resveratrol co-loaded NLC for the treatment of glioblastoma using intranasal delivery for brain targeting. Synergistic activity of temozolomide and resveratrol was determined using combination index method and 1:1 ratio was selected. QbD approach was used to formulate and optimize NLC, with minimum particle size, maximum transmittance and entrapment efficiency using Central Composite Rotable Design (CCRD) method. The optimized LTR-NLC had desired average particle size (209.3 nm), narrow PDI along, high percentage transmittance (>95%) and better entrapment efficiency (95.26% of TEM and 87.59% of RES). From ex-vivo permeation studies it was found that the permeation at 24 h was 77.43 %, and 88.55 % from LTR-NLC and 25.76 % and 31.10% from suspension for resveratrol and temozolomide respectively. In comparison to drug suspension, NLC had nearly 3-fold increase in drug penetration. IC50 value was also significantly better in the groups treated with LTR-NLC. Hence it can be concluded that LTR-NLC may be an effective formulation for the treatment of glioblastoma, according to the findings of this investigation.Copyright © 2023. Published by Elsevier B.V.