Abstract
BackgroundEfficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Accordingly, researches on polymeric nanomicelles continue to find suitable delivery systems. However, due to biocompatibility concerns, a few micellar nanoformulations have exquisitely been translated into clinical uses. Here, we report the synthesis of novel water-soluble nanomicelles using bioactive polyurethane (PU) polymer and efficient delivery of PTX in the human breast cancer MCF-7 cells.ResultsThe amphiphilic polyurethane was prepared through formation of urethane bounds between hydroxyl groups in poly (tetramethylene ether) glycol (PTMEG) and dimethylol propionic acid with isocyanate groups in toluene diisocyanate (TDI). The free isocyanate groups were blocked with phenol, while the free carboxyl groups of dimethylol propionic acid were reacted with triethylamine to attain ionic centers in the polymer backbone. These hydrophobic PTMEG blocks displayed self-assembly forming polymeric nanomicelles in water. The PTX loaded PU nanomicelles showed suitable physical stability, negative zeta potential charge (-43) and high loading efficiency (80%) with low level of critical micelle concentration (CMC). In vitro drug release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4, implying involvement of a pH-sensitive mechanism for drug release from the nanomicelles. The kinetic of release exquisitely obeyed the Higuchi model, confirming involvement of diffusion and somewhat erosion at pH 5.4. These nanomicelles significantly inhibited the growth and proliferation of the human breast cancer MCF-7 cells, leading them to apoptosis. The real time RT-PCR analysis confirmed the activation of apoptosis as result of liberation of cytochrome c in the cells treated with the PTX loaded PU nanomicelles. The comet assay analysis showed somewhat DNA fragmentation in the treated cells.ConclusionsBased upon these findings, we propose that the bioactive waterborne polyurethane nanomicelles can be used as an effective nanocarrier for delivery of anticancer chemotherapies such as paclitaxel.
Highlights
Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers
Strong absorptions at 1731 cm-1 (C = O stretching of urethane and carboxylic groups), 2850 and 2939 cm-1 (CH2 stretching vibrations of poly (tetramethylene ether) glycol (PTMEG) and toluene diisocyanate (TDI)), 1112 cm-1 (C-O-C stretching vibration of PTMEG), 3288 cm-1 (NH stretching), 1533 cm-1 (N-H bending) and 1210-1240 cm-1 confirmed the phenol blocked polyurethane dispersion (PBPUD) formation
In 1HNMR spectrum of polyurethane, the internal methylene groups of PTMEG and methyl groups of triethylammonium moieties were detected at 1.59 ppm
Summary
Efficient delivery of anticancer chemotherapies such as paclitaxel (PTX) can improve treatment strategy in a variety of tumors such as breast and ovarian cancers. Paclitaxel is an anticancer drug that has successfully been used against a variety of tumors such as ovarian and breast cancers [1] It is a lipophilic agent with limited solubility in water (0.3 μg/ml) [2], the most available injectable formulation of paclitaxel (i.e., Taxol®) has been formulated using mixture of Cremophor EL and ethanol (1:1 v/v). Such formulation was reported to induce serious undesired adverse reactions such as neurotoxicity and anaphylactic reactions due to high amount of Cremophor EL [3] that can alter the pharmacokinetics of PTX [4]. Having exploited passive targeting strategy based on EPR effects, the major objectives of these studies were to achieve a better pharmacokinetic profile with maximum efficiency in cancer cells and minimum toxicity in normal cells/ tissue
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