Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment

Abstract

Background Poly(L-γ-glutamylglutamine) paclitaxel (PGG-PTX) conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development. Methods and results PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid). The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment. Conclusion These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer.

Hydrophilic Fluorescent Nanoprodrug of Paclitaxel for Glioblastoma Chemotherapy

“…In U-87 MG cells, FONPs–PTX showed a lower inhibition of cell survival (concentration that inhibits 50% of cell survival IC 50 = 2.5 ± 0.1 μM) than PTX alone (IC 50 = 10.8 ± 1.6 nM), suggesting a delayed effect of the conjugate because of the time needed for intracellular enzymes to cleave PTX from nanoparticles, as previously observed. 7−9 Gomez et al have recently shown that PTX-coupled nitrogen-doped carbon nanodots by an ester bond exhibit a better anticancer activity compared to free PTX in several cell lines. 59 In our work, we demonstrated that PTX is not released from the prodrug in biological medium at 37 °C.…”

Identification of a pH-Responsive Peptide–Paclitaxel Conjugate as a Novel Drug with Improved Therapeutic Potential

“…The in vitro stability and drug release studies demonstrated that PTX was not released from the PDC adduct in biological mediums at 37 °C; rather, a sharp PTX release was observed at lower pH values (tumor microenvironment). Thus, we expected that the ester bond will break between PTX and CPP after cellular uptake, and the pharmacological properties of PTX on the microtubular network will not alter after its release . Therefore, we investigated the subcellular localization, intracellular delivery of the drug, the receptor-binding potential of the peptide, and the apoptosis-inducing pathway of our designed PDC in U87MG cells by using Cy5.5-PDC.…”

“…Thus, we expected that the ester bond will break between PTX and CPP after cellular uptake, and the pharmacological properties of PTX on the microtubular network will not alter after its release. 45 Therefore, we investigated the subcellular localization, intracellular delivery of the drug, the receptor-binding potential of the peptide, and the apoptosis-inducing pathway of our designed PDC in U87MG cells by using Cy5.5-PDC. The cells were treated with 10 nM Cy5.5-PDC for 1 h, washed with ice-cold PBS, further incubated for 4 h, and stained with Hoechst-33258 before images were acquired by an optical microscope.…”

Paclitaxel-Loaded Magnetic Nanoparticles Based on Biotinylated N-Palmitoyl Chitosan: Synthesis, Characterization and Preliminary In Vitro Studies

“…The obtained PTX-MN nanoparticles were characterized by infrared spectroscopy (Figure 3). The main infrared peaks of the PTX were registered at 3415-3310 cm −1 (N-H stretching vibrations), 2938 cm −1 (methylene stretching vibration), 1720 cm −1 (C=O stretching vibration of the ester groups), 1648 cm −1 (amide I), 1372 cm −1 (the C-N vibrations), 1071 cm −1 (C-O stretch), 982 cm −1 and 706 cm −1 (aromatic bonds) [26,27]. The FTIR spectrum of MN showed the characteristic bands for biotinylated N-palmitoyl chitosan at 3440 cm −1 (O-H, N-H stretch, imidazole ring of biotin), 2919 cm −1 and 2853 cm −1 (methylene and methyl groups stretching vibrations from palmitoyl chain), 1640 cm −1 and 1549 cm −1 (amide I), 1379 cm −1 (the C-N vibrations), 1067 cm −1 (C-O stretch) and for magnetite at 577 cm −1 (specific region for the Fe-O group).…”