Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

Abstract

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis

“…Figure 2D confirmed the smooth surface and the absence of pores. These results are consistent with the literature in which NCs were also prepared from PCL and by the chosen method [32][33][34][35][36][37][38]. In addition, no presence of drug crystal was reported on particle surface.…”

All-trans retinoic-acid inhibits heterodimeric bone morphogenetic protein 2/7-stimulated osteoclastogenesis, and resorption activity

“…Therefore BMP2/7 alone might even induce the osteoclast-mediated bone loss. Combined BMP2/7 and ATRA treatment by using local drug delivery approach such as BMP2/7 and ATRA loaded nanoparticles targeting bone niche might be better approach to treat both metastasized cancer and metastasis-caused osteolysis [ 40 ]. Similarly a combination of BMP2/7 and ATRA might be used for implant fixation in excessive bone resorbed implantation area via surface modified implants that can load BMP2/7 and ATRA, and release locally [ 41 ].…”

Poly(aspartic acid) in Biomedical Applications: From Polymerization, Modification, Properties, Degradation, and Biocompatibility to Applications

“…Fluorescent tagging of the liposomes showed that they accumulated mostly on the eroded bone surfaces. The optimum ASP repeating unit number was found to be from 4 to 10 for an effective bone–ASP interaction. − …”