Peptide-functionalized and high drug loaded novel nanoparticles as dual-targeting drug delivery system for modulated and controlled release of paclitaxel to brain glioma
International Journal of Pharmaceutics, ISSN: 0378-5173, Vol: 553, Issue: 1, Page: 169-185
2018
- 28Citations
- 42Captures
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Metrics Details
- Citations28
- Citation Indexes28
- CrossRef28
- 26
- Captures42
- Readers42
- 42
Article Description
A dual-targeting drug delivery system for paclitaxel (PTX) was developed by functionalizing novel polyester-based nanoparticles (NPs) with peptides possessing special affinity for low-density lipoprotein receptor (LDLR), overcoming the limitations of the current chemotherapeutics, to transport drug from blood to brain, and then target glioma cells. Employing novel biodegradable block co-polymers (P and 2P), PTX loaded and peptide-functionalized nanoparticles were prepared by a modified nano-co-precipitation method, carried out in one step only without emulsifier, allowing to obtain spherical nanometric (<200 nm), monodisperse (PDI ∼ 0.1), Poly (Ethylene Glycol) (PEG)-coated and high PTX loaded NPs with a slow and controlled release rate for a prolonged period of time. Peptide functionalization, confirmed by fluorimetric assay and HPLC amino acids analysis, enhanced the cellular uptake of functionalized-PTX-NPs by human primary glioblastoma cell line (U-87 MG) and Bovine Brain Endothelial Cells (BBMVECs), compared with non-functionalized-PTX-NPs. To confirm dual-targeting effect, transendothelial transport experiments in an in vitro BBB model and in vitro anti-tumoral activity against U-87 MG revealed that peptide-functionalized-PTX-NPs significantly increased the transport ratio of PTX across the BBB along with an improved anti-proliferative efficiency. Pharmacokinetics and biodistribution studies in rats, carried out by in vivo experiments with 125 I radiolabelled dual-targeting PTX-NPs, confirmed the stealthy behavior of NPs and indicated slightly lower levels of penetration into brain tissue in comparison with peptides known to be able to cross the BBB. These promising results suggested that the dual-targeting drug delivery system might have great potential for glioma therapy in clinical applications.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0378517318307580; http://dx.doi.org/10.1016/j.ijpharm.2018.10.022; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85055140494&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/30321641; https://linkinghub.elsevier.com/retrieve/pii/S0378517318307580; https://dx.doi.org/10.1016/j.ijpharm.2018.10.022
Elsevier BV
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