1. Gemcitabine-Phospholipid Complex Loaded Lipid Nanoparticles for Improving Drug Loading, Stability, and Efficacy against Pancreatic Cancer.
- Author
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Dora CP, Kushwah V, Yadav V, Kuche K, and Jain S
- Subjects
- Animals, Humans, Cell Line, Tumor, Mice, Particle Size, Apoptosis drug effects, Drug Carriers chemistry, Lipids chemistry, Drug Liberation, Male, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic pharmacokinetics, Antimetabolites, Antineoplastic chemistry, Antimetabolites, Antineoplastic pharmacology, Drug Stability, Rats, Liposomes, Gemcitabine, Deoxycytidine analogs & derivatives, Deoxycytidine chemistry, Deoxycytidine pharmacology, Deoxycytidine pharmacokinetics, Deoxycytidine administration & dosage, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Nanoparticles chemistry, Phospholipids chemistry
- Abstract
This study aims to encapsulate gemcitabine (GEM) using a phospholipid complex (PLC) in lipid nanoparticles (NPs) to achieve several desirable outcomes, including high drug loading, uniform particle size, improved therapeutic efficacy, and reduced toxicities. The successful preparation of GEM-loaded lipid NPs (GEM-NPs) was accomplished using the emulsification-solidification method, following optimization through Box-Behnken design. The size of the GEM-NP was 138.5 ± 6.7 nm, with a low polydispersity index of 0.282 ± 0.078, as measured by a zetasizer and confirmed by transmission electron and atomic force microscopy. GEM-NPs demonstrated sustained release behavior, surpassing the performance of the free GEM and phospholipid complex. Moreover, GEM-NPs exhibited enhanced cytotoxicity, apoptosis, and cell uptake in Panc-2 and Mia PaCa cells compared to the free GEM. The in vivo pharmacokinetics revealed approximately 4-fold higher bioavailability of GEM-NPs in comparison with free GEM. Additionally, the pharmacodynamic evaluation conducted in a DMBA-induced pancreatic cancer model, involving histological examination, serum IL-6 level estimation, and expression of cleaved caspase-3, showed the potential of GEM-NPs in the management of pancreatic cancer. Consequently, the lipid NP-based approach developed in our investigation demonstrates high stability and uniformity and holds promise for enhancing the therapeutic outcomes of GEM.
- Published
- 2024
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