Abstract
Development of nanocarrier-based drug delivery systems is a major breakthrough in pharmacology, promising targeted delivery and reduction in drug toxicity. On the cellular level, encapsulation of a drug substantially affects the endocytic processes due to nanocarrier–membrane interaction. In this study we synthesized and characterized nanocarriers assembled from amphiphilic oligomers of N-vinyl-2-pyrrolidone with a terminal thiooctadecyl group (PVP-OD). It was found that the dissolution free energy of PVP-OD depends linearly on the molecular mass of its hydrophilic part up to = 2 × 104, leading to an exponential dependence of critical aggregation concentration (CAC) on the molar mass. A model hydrophobic compound (DiI dye) was loaded into the nanocarriers and exhibited slow release into the aqueous phase on a scale of 18 h. Cellular uptake of the loaded nanocarriers and that of free DiI were compared in vitro using glioblastoma (U87) and fibroblast (CRL2429) cells. While the uptake of both DiI/PVP-OD nanocarriers and free DiI was inhibited by dynasore, indicating a dynamin-dependent endocytic pathway as a major mechanism, a decrease in the uptake rate of free DiI was observed in the presence of wortmannin. This suggests that while macropinocytosis plays a role in the uptake of low-molecular components, this pathway might be circumvented by incorporation of DiI into nanocarriers.
Highlights
The use of nanotechnology methods in drug delivery opens fundamentally new possibilities for regulating the concentration and exposure of an active component to pharmacological targets
The number average molecular weight Mn required for application of PVP-OD as drug carrier is in the range of 103–104, which corresponds to the number average degree of polymerization from about 9 to 90
With an increase in the number average molecular weight of the hydrophilic fragment the solubility of PVP-OD increases as expected, which is manifested in an increase in the critical aggregation concentration (CAC)
Summary
The use of nanotechnology methods in drug delivery opens fundamentally new possibilities for regulating the concentration and exposure of an active component to pharmacological targets. This paper is focused on the in vitro uptake of synthetically available and non-toxic aggregates of amphiphilic oligomers of PVP-OD loaded with DiI dye used as a model hydrophobic drug by human glioblastoma (U87) and fibroblasts (CRL 2429). For synthesized PVP-ODs, a linear dependence of the inversed number average molecular weight M−n 1 as a function of n-octadecyl mercaptan concentration C(C18H37SH) was observed (Figure 2).
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