Intranasal Delivery of Ligand‐Conjugated NLCs Co‐Loaded With Docetaxel and Quercetin: HPLC Method Development, Pharmacokinetics, and Brain Biodistribution in Wistar Rats for Glioblastoma

Glioblastoma multiforme (GB) is the most aggressive type of brain cancer, with treatment hindered by ineffective drug delivery across the blood–brain barrier and systemic side effects. Nanostructured lipid carriers (NLCs) are innovative nanocarriers that can improve drug solubility, stability, and targeted delivery to the brain. (DX–QR) NLC was developed and optimized using a modified emulsification‐sonication method and a central composite rotatable design. Surface conjugation of (DX–QR) NLC with transferrin (Tf) was achieved through carbodiimide chemistry resulting in the formulation of Tf‐(DX–QR) NLC. A high‐performance liquid chromatography (HPLC) method was established and validated according to ICH Q2(R1) standards for simultaneous measurement of docetaxel (DX) and quercetin (QR) in plasma, brain tissue, and other organs of Wistar rats. Using a Shim‐pack Solar C18 column and an acetonitrile‐water (60:40) mobile phase at a 242 nm wavelength, the method demonstrated linearity ( R 2 > 0.9900), along with accuracy, precision, and recovery rates > 98%. The developed method was used to evaluate the pharmacokinetics and biodistribution of DX and QR, indicating that intranasal (IN) administration of Tf‐(DX–QR) NLC resulted in brain concentrations of DX (4.6‐fold) and QR (8.8‐fold) higher than those achieved through (DX–QR) suspension delivered via intravenous (IV) and IN, highlighting their potential as noninvasive, effective, and targeted treatments for GB.