Paclitaxel-loaded polyphosphate nanoparticles: a potential strategy for bone cancer treatment

Abstract

While it has been shown that phosphates can target molecules and nanocarriers to bone we herein demonstrate the preparation of polyphosphate nanoparticles loaded with paclitaxel using a simple miniemulsion/solvent-evaporation technique as a model for chemotherapeutic delivery. Polyphosphates exhibit much higher structural versatility, relying on the pentavalence of the phosphorus center compared to conventional polyesters. This versatility allows for the development of new degradable polymeric carriers with inherent bone adhesion ability by the interaction of the nanoparticles with a calcium phosphate material used for bone regeneration. The novel polyphosphate nanoparticles were investigated in detail with respect to their size distribution, zeta-potential, thermal and morphological properties and were further proven to be efficiently loaded with a hydrophobic drug (up to 15 wt%). The in vitro cytotoxicity was assessed against human cancer cell lines (HeLa and Saos-2), and the paclitaxelloaded nanoparticles showed a similar cytotoxicity profile similar to the commercially available formulation Taxomedac® and the pure paclitaxel for loading ratios of 10 wt% but additionally proved efficient adhesion on calcium phosphate granules allowing drug delivery to bone. This first report demonstrates that polyphosphate nanoparticles are promising materials for the development of systemic or local bone cancer treatment, even by direct application or by formation of composites with calcium phosphate cements.

Phosphodiester Hydrogels for Cell Scaffolding and Drug Release Applications

“…ADMET is an attractive alternative approach. However, the residues of potentially toxic heavy metal catalysts can be a cause for concern . Moreover, the majority of known polymerization routes end up with linear polymers instead of hydrogels.…”

Hyperbranched polyphosphates: synthesis, functionalization and biomedical applications

“…According to the side group connected to the phosphorous atom, these polymers are classified as polyphosphate, polyphosphonate, polyphosphite, or polyphosphoramidate (Fig. 19 In recent years, the synthesis and functionalization of polyphosphates is still a popular topic that have been explored by many groups, such as Wang, 20 Wooley, 21,22 Wurm, 23 Momekov, 24 Ni, 25 Iwasaki, 26 and Yang. To prepare polymer-inorganic hybrid materials and mimic biomineralization, Penczek et al pioneered the synthesis of polyphosphoesters at the end of the 1970s.…”

Poly(phosphonate)-mediated Horner–Wadsworth–Emmons reactions

“…[16][17][18][19][20] Several reaction conditions have been reported to prepare polymers for applications in lubricants, optics, medicine and, most importantly, as flame-retardant additives. 27,28 Nevertheless, the alkyl side-chain in these systems remain untouched and unreactive, which is beneficial for biomedical applications and a controlled degradation behavior. ADMET of acyclic unsaturated phosphonates yields hydrophobic materials that show similar bone-targeting properties as their phosphate counterparts.…”

“…27,28,[35][36][37][38] Tailoring these properties allowed us to enhance the HWE reaction and its workup procedure in several model reactions. 27,28,[35][36][37][38] Tailoring these properties allowed us to enhance the HWE reaction and its workup procedure in several model reactions.…”

“…27,28,35,36,38 With this report we introduce this material into the organic-chemical science and give chemists and researchers an adjustable and versatile tool to improve their synthesis in the lab and industry. In addition, this is the first report on the synthesis of linear poly (hydroxyalkylene phosphate)s from poly(alkylalkylene phosphonate)s. In our current and past work on this versatile class of materials we have demonstrated the usability of poly( phosphonate)s in materials science and the biomedical field.…”