Original ArticleOptimizing particle size of docetaxel-loaded micelles for enhanced treatment of oral epidermoid carcinoma
Graphical Abstract
Five micelles (30-230 nm) based on methoxy poly(ethylene glycol)-poly(lactide) copolymers and one size/charge-changing micelle based on amphiphilic poly(β-amino ester) derivates were prepared for the investigation of size effects. Through rational design of the particle size, an optimal micellar formulation of docetaxel with prolonged circulation time, improved intratumoral penetration, and enhanced cellular uptake was obtained to impede the tumor growth effectively.
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Materials, cell lines, and animals
Monomethoxy poly(ethylene glycol) (MPEG, Mn: 2000 and 5000), 3-amino-1-propanol, and stannous octoate (Sn(Oct)2) were purchased from Sigma (USA). D, L-Lactide was purchased from Shandong Institute of Medical Instruments (Ji'nan, China). Docetaxel was obtained from Hisun Pharmaceutical Co., Ltd. (Hangzhou, China). 1,1'-Dioctadecyl-3,3,3',3'- tetramethylindotricarbocyanine iodide (DiR), a near-infrared dye, was purchased from Biotium (Invitrogen, USA). Curcumin (CUR), acryloyl chloride, and 1,
Synthesis and characterization of copolymers
A series of MPEG-PLA copolymers were synthesized with fixed PEG blocks (5000 Da) and PLA block of varying lengths. Using the 1H NMR spectra (Figure S1), the molecular weight of PLA block for each copolymer was calculated by the integrals of the peaks corresponding to the PEG methylene protons (CH2, δ 3.7 ppm) and the PLA methyne protons (CH, δ 5.1 ppm) (Table 1). The route of synthesis of MPEG-PLA-PAE is illustrated in Figure 1. Compared with the 1H NMR spectra of MPEG-PLA, new peaks at 1.70,
Discussion
There are three major phases in nanoparticle drug delivery: systemic circulation, intratumoral penetration, and interaction with tumor cells. It is believed that particle size is a major attribute influencing the design of nanoparticulate systems. Thus, in this study, the effect of particle size on the interactions between nanoparticles and biological systems in relation to these three phases was examined to determine how particle design could be optimized for efficient cancer therapy.
During
References (28)
- et al.
Polymer therapeutics: Clinical applications and challenges for development
Adv Drug Deliv Rev
(2009) Nanoparticles in drug delivery: Past, present and future
Adv Drug Deliv Rev
(2013)Polymer therapeutics as nanomedicines: New perspectives
Curr Opin Biotechnol
(2011)- et al.
Lipids-based drug carrier systems by dense gas technology: A review
Chem Eng J
(2012) - et al.
Challenges associated with penetration of nanoparticles across cell and tissue barriers: A review of current status and future prospects
Nano Today
(2014) - et al.
The effect of PEG-5 K grafting level and particle size on tumor accumulation and cellular uptake
Int J Pharm
(2013) - et al.
Size and shape effects in the biodistribution of intravascularly injected particles
J Control Release
(2010) - et al.
The anti-tumor efficacy of curcumin when delivered by size/charge-changing multistage polymeric micelles based on amphiphilic poly(β-amino ester) derivates
Biomaterials
(2014) - et al.
Polymeric nanoparticles of different sizes overcome the cell membrane barrier
Eur J Pharm Biopharm
(2013) - et al.
pH-responsive and charge shielded cationic micelle of poly(l-histidine)-block-short branched PEI for acidic cancer treatment
J Control Release
(2013)
In vivo tumor targeting of tumor necrosis factor-α-loaded stealth nanoparticles: Effect of MePEG molecular weight and particle size
Eur J Pharm Sci
Image-based analysis of the size- and time-dependent penetration of polymeric micelles in multicellular tumor spheroids and tumor xenografts
Int J Pharm
Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium
Biophys J
Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway
Biomaterials
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Conflict of interest statement: No conflict of interest is reported by the authors of this paper.
Funding sources: This work was supported by National Natural Science Funds for Excellent Young Scholar (81222047).