Preparation, characterization, and in vitro activity evaluation of triblock copolymer-based polymersomes for drugs delivery
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Polymersomes are polymer-based vesicles that form upon hydration of amphiphilic block copolymers and display high stability and durability, due to their mechanical and physical properties. They have hydrophilic reservoirs as well as thick hydrophobic membranes; allowing to encapsulate both water-soluble bioactive agent and hydrophobic drugs. In this study, poly ethylene glycol (PEG3350 and PEG6000) were used as hydrophilic part and poly(vinyl benzoate) (PVBz) as hydrophobic block to synthesize amphiphilic triblock copolymers (PVBz-b-PEG-b-PVBz). Different proportions of hydrophilic/hydrophobic part were assayed in order to obtain polymersomes by solvent injection method. For the synthesis of the copolymers, the initial block of PEG was derived to obtain a macroinitiator through a xanthate functional group (PEGX3 or PEGX6) and the polymerization of vinyl benzoate was carried out through reversible addition-fragmentation chain transfer polymerization (RAFT). The structure of PEGX and copolymers was confirmed by Infrared, 1H-NMR and UV-Vis spectrometry, while the average molecular weight (Mw) and polydispersity index (PI) were determined by size exclusion chromatography (SEC). The structures adopted by the copolymers in aqueous solution by self-assembly were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Both techniques confirm that polymersomes were obtained for a fraction of hydrophilic block (f) ≈ 35 ± 10%, with a diameter of 38.3 ± 0.3 nm or 22.5 ± 0.7 nm, as determined by TEM and according to the M w of the precursor block copolymer. In addition, we analyzed the possible cytotoxicity in view of its potential application as biomedical nanocarrier. The results suggest that polymersomes seem not induce cytotoxicity during the periods of time tested.
KeywordsTriblock copolymer Polymersomes Self-assembly Cytotoxicity Nanomedicine
LNB is a fellowship of CONICET, AMC is a member of the Carrera del Investigador Científico CICPBA, and PP and MSC are members of the Carrera del Investigador CONICET and Professors of UNLP.
This research was partially supported by grants from the Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP, 11/X768 and 11/X769), Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Consejo Nacional de Investigación Científicas y Técnicas (CONICET) (PIP-D0047), and LNLS (Brazilian Synchrotron Light Laboratory, Brazil—proposal 20170091).
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Conflict of interest
The authors declare that they have no conflicts of interests.
- Colley HE, Hearnden V, Avila-Olias M, Cecchin D, Canton I, Madsen J, MacNeil S, Warren N, Hu K, McKeating JA, Armes SP, Murdoch C, Thornhill MH, Battaglia G (2014) Polymersome-mediated delivery of combination anticancer therapy to head and neck cancer cells: 2D and 3D in vitro evaluation. Mol Pharm 11:1176–1188CrossRefGoogle Scholar
- Davidson GS, Terbrugge KG (1995) Histologic long-term follow-up after embolization with polyvinyl alcohol particles. Am J Neuroradiol 16:843–846Google Scholar
- Guinier AF, Fournet G (1955) Small angle scattering of X-rays. Wiley, New YorkGoogle Scholar
- Lastra ML, Molinuevo MS, Cortizo AM, Cortizo MS (2017) Fumarate copolymer-chitosan cross-linked scaffold directed to osteochondrogenic tissue engineering. Macromol Biosci 17. https://doi.org/10.1002/mabi.201600219
- Working PK (1997) Safety of poly(ethylene glycol) and poly(ethylene glycol) derivatives. In Poly(ethylene glycol)chemistry and biological applications, eds Harris JM, Zalipsky S, (ACSC, Symposium Series 680) Ch 4, pp 45–57Google Scholar