Synthesis of degradable polyphosphoester copolymers for templating calcium carbonate drug delivery carriers

The design of drug delivery systems (DDS) often requires biodegradable and biocompatible materials that allow safe retention and controlled release of the drug. In this respect, CaCO3 particles are appropriate drug carriers that have excellent properties such as low density, high specific surface areas and porosity for drugs and proteins encapsulation. Here, hyaluronic acid usually used for templating CaCO3 particles was substituted by a degradable synthetic copolymer based on PPE. The latter is a promising candidate due to its biocompatibility, biodegradability and the low toxicity of its degradation products such as phosphates. We also introduced acid functions on the PPE segment in order to enhance its calcium affinity and ability to tune the morphology of the CaCO3 particles.

The butynyl phospholane (BYP) polymerization was initiated from poly(ethylene oxide) PEO-OH by organocatalyzed ring opening polymerization (ROP) [2] followed by UV catalyzed thiol-yne addition of 3-mercaptopropionoic acid onto the alkyne functions. CaCO3 particles were then generated in the presence of the copolymer following a procedure inspired from .

Well-defined PPE copolymers bearing pendant alkynyl groups, i.e. PEO-b-PBYP (Ð <1.1), were obtained by organocatalyzed ROP of BYP initiated at 0°C from PEO-OH (Scheme 1). The copolymer was then reacted under UV with 3-mercaptopropionoic acid in order to introduce carboxylic acid functions along the PPE backbone by thiol-yne reaction. NMR analyses confirmed that full functionalization was reached after 2h. The high density of acid moieties in PEO-b-PBYP(COO-)2 is supposed to facilitate the Ca2+ complexation.

The solution behavior and self-assembly of PEO-b-PBYP(COO-)2 in water was investigated by DLS with and without Ca+2 at different pH. Finally, stoichiometric amounts of CaCl2 and Na2CO3 were mixed in water containing the PEO-b-PBYP(COO-)2 which strongly influences the size of the CaCO3 particles (~1.5 µm).

The acid-bearing PPE-based copolymers were successfully prepared and used as templating agents for the synthesis of CaCO3 particles.