Abstract
Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN—glycerol monostearate, GM, as the lipid and ATO5-SLNs—glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of electroporation improved the transport of encapsulated and free C6 into both treated cell lines.Electronic supplementary materialThe online version of this article (doi:10.1007/s00232-016-9906-1) contains supplementary material, which is available to authorized users.
Highlights
One of the main objectives of nanomedicine technology is the delivery of poorly soluble drugs and/or supporting their bioavailability, improvement of drug targeting to the target cells with simultaneously reduced toxicity of normal cells, and additional control of the location and the rate of drug release
Tween 80 (T80), which was used as a non-ionic surfactant, tetrahydrofuran (THF), and coumarin 6 (C6; 3-(20-benzothiazolyl)-7-diethylaminocoumarin; structure shown in Fig. 1) were purchased from Sigma-Aldrich
It can be concluded that the solid lipid nanoparticles (SLNs) dispersions displayed an average size of 380 nm of diameter for glycerol monostearate (GM) used as a lipid, and 550 nm—for ATO5
Summary
One of the main objectives of nanomedicine technology is the delivery of poorly soluble drugs and/or supporting their bioavailability, improvement of drug targeting to the target cells with simultaneously reduced toxicity of normal cells, and additional control of the location and the rate of drug release. Nanosized carriers are currently regarded as one of the most promising directions in pharmaceutical research. They allow encapsulation of a complex cargo and its selective delivery to cells, enabled with a variety of carrier surface modifications (Lamch et al 2014; Bazylinska et al 2012, 2014a, b; Paliwal et al 2014; Tran et al 2014; de Morais et al 2014; Saadeh et al 2014). The research of liposomes showed that both positive and negative charges could enhance the delivery of liposomes to cells through adsorptive endocytosis and the extension of the half-life clearance of liposomes from the blood. Zeta potential of liposomes or nanoparticles is an important factor for their cytotoxicity, and in some cases, cationic charge is demanded to increase the cytotoxicity (Liu et al.2012; Muller et al 2001)
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