Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel
The management of retinoblastoma (RB) involves the use of invasive treatment regimens. Paclitaxel (PTX), an effective antineoplastic compound used in the treatment of a wide range of malignant tumors, poses treatment challenges due to systemic toxicity, rapid elimination, and development of resistance. The goal of this work was to develop PTX-loaded, α-tocopherol succinate (αTS)-based, nanostructured lipid carrier (NLCs; αTS-PTX-NLC) and PEGylated αTS-PTX-NLC (αTS-PTX-PEG-NLC) to improve ocular bioavailability. The hot homogenization method was used to prepare the NLCs, and repeated measures ANOVA analysis was used for formulation optimization. αTS-PTX-NLC and αTS-PTX-PEG-NLC had a mean particle size, polydispersity index and zeta potential of 186.2 ± 3.9 nm, 0.17 ± 0.03, −33.2 ± 1.3 mV and 96.2 ± 3.9 nm, 0.27 ± 0.03, −39.15 ± 3.2 mV, respectively. The assay and entrapment efficiency of both formulations was >95.0%. The NLC exhibited a spherical shape, as seen from TEM images. Sterilized (autoclaved) formulations were stable for up to 60 days (last time point checked) under refrigerated conditions. PTX-NLC formulations exhibited an initial burst release and 40% drug release, overall, in 48 h. The formulations exhibited desirable physicochemical properties and could lead to an effective therapeutic option in the management of RB.
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Materials
PTX (99.5%), Lot no. P05F047 was purchased from Alfa AESAR, Haverhill, MA, αTS (RRR-α-Tocopheryl acid succinate) was purchased from Spectrum® Chemical Mfg Corp., New Bruinswick, NJ, USA, Lot no. 2HE0577; Propylene glycol monocaprylate (Capryol™ 90) was a gift sample given by Gattefossé, France, Batch number 16093. N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (DSPE-PEG-2k) was purchased from Lipoid GmbH (Ludwigshafen, Germany). All other reagents were of high-performance liquid chromatography (HPLC) analytical grade.
Also used in the research: Tween®80, Poloxamer® 188
Marathe, S.; Shadambikar, G.; Mehraj, T.; Sulochana, S.P.; Dudhipala, N.; Majumdar, S. Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel. Pharmaceutics 2022, 14, 1034. https://doi.org/10.3390/pharmaceutics14051034