Double hydrophilic polyphosphoester containing copolymers as efficient templating agents for calcium carbonate microparticles

Abstract

The use of calcium carbonate (CaCO 3 ) microparticles is becoming more and more attractive in many fields especially in biomedical applications in which the fine tuning of the size, morphology and crystalline form of the CaCO 3 particles is crucial. Although some structuring compounds, like hyaluronic acid, give satisfying results, the control of the particle structure still has to be improved. To this end, we evaluated the CaCO 3 structuring capacity of novel well-defined double hydrophilic block copolymers composed of poly(ethylene oxide) and a polyphosphoester segment with an affinity for calcium like poly(phosphotriester)s bearing pendent carboxylic acids or poly(phosphodiester)s with a negatively charged oxygen atom on each repeating monomer unit. These copolymers were synthesized by a combination of organocatalyzed ring opening polymerization, thiol-yne click chemistry and protection/ deprotection methods. The formulation of CaCO 3 particles was then performed in the presence of these block copolymers (i) by the classical chemical pathway involving CaCl 2 and Na 2 CO 3 and (ii) by a process based on supercritical carbon dioxide (scCO 2 ) technology in which CO 3 2À ions are generated in aqueous media and react with Ca 2+ ions. Porous CaCO 3 microspheres composed of vaterite nanocrystals were obtained. Moreover, a clear dependence of the particle size on the structure of the templating agent was emphasized. In this work, we show that the use of the supercritical process and the substitution of hyaluronic acid for a carboxylic acid containing copolymer decreases the size of the CaCO 3 particles by a factor of 6 (B1.5 mm) while preventing their aggregation.

Functional biodegradable polymers via ring-opening polymerization of monomers without protective groups

“…Frank and coworkers used D2 to form anionic hydrophilic PPE-copolymers as efficient templating agent for calcium carbonate particles. 324,325 Wang and coworkers 326 reported a cyclic phosphate carrying an allyl pendant group (2-(prop-2-en-1-yloxy)-2-oxo-1,3,2-dioxaphospholane, D3), which was polymerized with a PEG-macroinitiator. The block copolymers self-assembled into nanoparticles and the allyl groups were post-modified by thiol-ene reaction with cysteamine and partially further reacted with dimethyl maleic anhydride to introduce pH-responsivity.…”

Osteogenic Differentiation of Human Adipose Tissue-Derived MSCs by Non-Toxic Calcium Poly(ethylene phosphate)s

“…However, in the strict sense, these polymers are not biodegradable. The second type of these prospective polymers can be prepared by the ring-opening polymerization (ROP) of cyclic ethylene phosphate monomers [20][21][22][23][24] followed by the transformation of poly(ethylene phosphate)s to poly(ethylene phosphoric acid)s (PEPA) or their salts [25][26][27][28][29][30][31] (Scheme 1b). The mild thermolysis of the polymers of tert-butyl ethylene phosphate ( t BuOEP) was found to be a simple and efficient method of PEPA preparation (Scheme 1c) [32,33].…”

Bone Mineral Affinity of Polyphosphodiesters

“…Penczek and coworkers [26,27] synthesized the triblock copolymer poly(ethylene glycol)-poly(alkylene phosphate)-poly(ethylene glycol) and found that it modulated the crystallization of CaCO 3 particles, resulting in the formation of unique features consisting of semi-open empty spheres that were composed of small crystallites with a diameter of 40-90 nm. Christine et al also studied the templating capacity of PPDEs for the synthesis of CaCO 3 particles [28]. [29].…”