A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

Abstract

The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX:DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in the in vitro experiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.

Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo

“…Under this circumstance, the safety of these SMMDC NPs might be improved because they possess surfactant-free and organic solvent-free characteristics. 12 In the present research, the MTD value of NPPA-PTX@PEG NPs in healthy ICR mice was almost sixfold than that of Taxol, indicating that the safety of NPPA-PTX@ PEG NPs was significantly enhanced compared to Taxol. We previously demonstrated that the XlogP and Hansen solubility parameters are key factors for predicting SMMDCs self-assembling into NPs.…”

“…Interestingly, these can self-assemble into NPs in water, and their antitumor activity has been confirmed in vitro and in vivo; 11 eg, conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) can self-assemble into NPs. 12 These SMMDC NPs, with higher drug loading and an aqueous solvent with organic solventfree characteristics, can be prepared by a simple precipitation method. 11 The theoretical partition coefficient (XlogP) and Hansen solubility parameters of the SMMDCs might be the key factors for forming self-assembled NPs.…”

“…The preparation method of NPPA-PTX@PEG NPs is by a simple precipitation, similar to our CLA-PTX@ PEG NPs preparation. 12 The drug loading of NPPA-PTX in NPPA-PTX@PEG NPs was ~90% (w/w) with CrEL-free and organic solvent-free characteristics. As the ratio of NPPA-PTX: DSPE-PEG was only 1:0.1 (w/w), these as-prepared NPPA-PTX@PEG NPs could be regarded as possessing carrier-free or drug-self carrier characteristics.…”

Lymph cancer chemotherapy: delivery of doxorubicin-gemcitabine prodrug and vincristine by nanostructured lipid carriers

“…There are many nanosystems that can be used to deliver cancer drugs, including cross-linked self-assembly nanoparticles, polymersomes, liposomes, and others. [42][43][44][45] Nanocarriers using lipids to load drugs form a carrier system with a number of desirable features, including a low toxicity, a biodegradable particulate matrix, nontoxic degradation products, a high capacity to incorporate lipophilic and hydrophilic drugs, a controlled release of the incorporated drug, and easy scale-up at low cost. 46 For this purpose, different types of lipid carriers, including lipid-drug conjugates, SLNs, and NLCs, have been developed.…”

The theranostic efficiency of tumor-specific, pH-responsive, peptide-modified, liposome-containing paclitaxel and superparamagnetic iron oxide nanoparticles

“…The in vitro antitumor activity of PTX/SPIO-SSL-H 7 K(R 2 ) 2 was evaluated in MDA-MB-231 cell line following our previously reported method. 23,24,[28][29][30][31] Briefly, MDA-MB-231 cells (1×10 4 cells/well) were seeded in 96-well plates and incubated for 24 h. Then, the cells were treated with cell culture medium (pH 6.8 or pH 7.4) containing different amounts of PTXloaded liposomes and incubated for 48 h at 37°C. The cell viability was determined by sulforhodamine B assay.…”