Micelle-templated, poly(lactic-co-glycolic acid) nanoparticles for hydrophobic drug delivery
Gauri M Nabar,1 Kalpesh D Mahajan,1 Mark A Calhoun,2 Anthony D Duong,1 Matthew S Souva,1 Jihong Xu,3,4 Catherine Czeisler,5 Vinay K Puduvalli,3,4 José Javier Otero,5 Barbara E Wyslouzil,1,6 Jessica O Winter1,2 1William G Lowrie Department of Chemical and Biomolecular Engineering, 2Depart...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2018
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/8a2a798c9805434d8bdb18c5c7075bf1 |
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| Sumario: | Gauri M Nabar,1 Kalpesh D Mahajan,1 Mark A Calhoun,2 Anthony D Duong,1 Matthew S Souva,1 Jihong Xu,3,4 Catherine Czeisler,5 Vinay K Puduvalli,3,4 José Javier Otero,5 Barbara E Wyslouzil,1,6 Jessica O Winter1,2 1William G Lowrie Department of Chemical and Biomolecular Engineering, 2Department of Biomedical Engineering, 3Division of Neuro-oncology, College of Medicine, The Ohio State University Comprehensive Cancer Center, 4Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurosurgery, College of Medicine, The Ohio State University Comprehensive Cancer Center, 5Department of Pathology and the Neurological Research Institute, College of Medicine, 6Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA Purpose: Poly(lactic-co-glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches.Methods: Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, “PolyDots”), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles.Results: PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS-b-PEO micelles (ie, ~7%). Increasing the PLGA:PS-b-PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray.Conclusion: Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications. Keywords: PLGA, nanoparticles, micelles, drug delivery, hydrophobic drug, block copolymer, glioma, electrospray |
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