期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 608, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121120
关键词
Polylactic acid-polyethylene glycol nano-particles; Orthogonal characterization; Pharmacokinetics; Prolonged and sustained delivery system
By optimizing PLA isomer and molecular weight of PLA-PEG NPs, it was found that SC-PEG NPs (12k-5k) had the most compact structure, highest PEG density, best drug loading content, and lowest surface adsorption. This makes them promising drug carriers for sustained and prolonged delivery of tamoxifen.
To optimize prolonged and sustained delivery of polylactide-block-polyethyleneglycol polymeric nanoparticles (PLA-PEG NPs), in terms of the PLA isomer and molecular weight, we performed orthogonal physicochemical characterization and evaluated the pharmacokinetics of tamoxifen (TAM)-loaded PLA-PEG NPs. DL-lactide-(DL PEG NP), L-lactide-(L-PEG NPs), and stereocomplex-based (SC-PEG NPs) PLA-PEGs, with two different PLA to PEG ratios (12k-5k and 5k-5k Da) were synthesized, and NPs were prepared by anti-solvent precipitation. Size exclusion chromatography, multi-angle light scattering, dynamic light scattering, and H-1 nuclear magnetic resonance studies revealed that SC-PEG NPs (12k-5k) had a compact structure and the highest PEG density, followed by L-PEG NPs (12k-5k), DL-PEG NPs (12k-5k), and all PLA-PEG NPs (5k-5k). Additionally, solid-phase extraction indicated that SC-PEG NPs (12k-5k) had the highest drug loading content and the lowest surface TAM adsorption, of the PLA-PEGs evaluated. These results were explained by the crystallinity of the PLA core, which was analyzed by X-ray diffraction. In the pharmacokinetic studies, C-14-TAM-loaded In-111-SC-PEG NPs (12k-5k) exhibited the highest area under the plasma concentration-time curve, followed by L-PEG NPs (12k-5k) and DL PEG NPs (12k-5k), after intravenous injection in mice. These results indicate that SC-PEG NPs (12k-5k) are promising drug carriers for the sustained and prolonged delivery of TAM.
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