ABSTRACT
Purpose
For nanocarrier-based targeted delivery systems, preventing phagocytosis for prolong circulation half life is a crucial task. PEGylated poly(n-butylcyano acrylate) (PBCA) NP has proven a promising approach for drug delivery, but an easy and reliable method of PEGylation of PBCA has faced a major bottleneck.
Methods
PEGylated PBCA NPs containing docetaxel (DTX) by modified anionic polymerization reaction in aqueous acidic media containing amine functional PEG were made as an single step PEGylation method. In vitro colloidal stability studies using salt aggregation method and antiopsonization property of prepared NPs using mouse macrophage cell line RAW264 were performed. In vitro performance of anticancer activity of prepared formulations was checked on MCF7 cell line. NPs were radiolabeled with 99mTc and intravenously administered to study blood clearance and biodistribution in mice model.
Results
These formulations very effectively prevented phagocytosis and found excellent carrier for drug delivery purpose. In vivo studies display long circulation half life of PBCA-PEG20 NP in comparison to other formulations tested.
Conclusions
The PEGylated PBCA formulation can work as a novel tool for drug delivery which can prevent RES uptake and prolong circulation half life.
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Abbreviations
- DTX:
-
docetaxel
- EPR:
-
enhanced permeation and retention
- NP:
-
nanoparticle
- PBCA:
-
poly(n-butylcyano acrylate)
- PEG:
-
polyethylene glycol
- PMN:
-
polymorphonuclear cells
- RES:
-
reticuloendothelial system
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ACKNOWLEDGMENTS & DISCLOSURES
This research was supported by National Doctoral Fellowship by All India Council of Technical Education (AICTE) (1-10/RID/NDF-PG/(39)2008-2009), India. The authors are also thankful to Tong Shen Enterprise, Taiwan, for providing a free gift sample of n-butyl cyanoacrylate monomer.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s11095-011-0565-8
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Figure S-1
Fourier transform spectroscopy (FTIR) reports of PBCA-PEG, PBCA and PEG polymer. (JPEG 50 kb)
Figure S-2
H1 Nuclear magnetic resonance (NMR) reports of PBCA-PEG polymer of PBCA-PEG20 NP. (JPEG 29 kb)
Figure S-3
Gel Permeation Chromatography (GPC) reports of PBCA NP and PBCA-PEG20 NP. (JPEG 37 kb)
Table SI
% Release of 6-coumarin from PBCA NP and PEGylated PBCA NP using PBS (pH 7.4) with 0.5% tween after 6 h. (DOCX 10 kb)
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Chaudhari, K.R., Ukawala, M., Manjappa, A.S. et al. Opsonization, Biodistribution, Cellular Uptake and Apoptosis Study of PEGylated PBCA Nanoparticle as Potential Drug Delivery Carrier. Pharm Res 29, 53–68 (2012). https://doi.org/10.1007/s11095-011-0510-x
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DOI: https://doi.org/10.1007/s11095-011-0510-x