One‐Pot Polymerization Syntheses: Incorporating Bioactives into Poly(anhydride‐esters)

Abstract

To reduce raw material consumption and increase synthetic efficiency, bioactive‐based poly(anhydride‐esters) containing aliphatic dicarboxylic acid‐linkages and bioactives, salicylic and p‐hydroxybenzyl acid, are synthesized via one‐pot melt‐condensation polymerizations. One‐pot poly(anhydride‐esters) physicochemical characteristics, molecular weight, and thermal properties are analyzed and compared. One‐pot salicylic acid‐based poly(anhydride‐esters) are further evaluated against analogous polymers synthesized via established methods, possessing statistically similar polymer and thermal properties while drastically reducing reaction time and solvent usage. Interestingly, p‐hydroxybenzyl acid‐based poly(anhydride‐ester) synthesis is temperature‐dependent, as higher reaction temperatures facilitate polyester formation. Compared to their poly(anhydride‐ester) analogs, these are found to possess improved thermal properties and higher molecular weight while. Accelerated hydrolytic degradation studies confirm complete bioactive release and polymer degradation. Furthermore, polymer cytotoxicity studies using 3T3 mouse fibroblasts show all polymers to be cytocompatible above therapeutically relevant concentrations. This method demonstrates that the synthesis of high‐yielding monomers can be followed by melt‐condensation polymerization in situ for the synthesis of polyanhydrides and their derivatives.

Hyperbranched poly (ester) s for delivery of small molecule therapeutics

“…The suspended conjugate particles were probably eroded from the outside in by enzyme catalysis giving rise to zero order kinetics for the release of salicylic acid. This type of kinetics has been observed for similar systems …”

“…The time‐release of salicylic acid would enhance the duration of its effectiveness while minimizing skin irritation. Due to the problems associated with the administration of salicylic acid derivatives, much effort has been directed toward the development of biodegradable polymeric drug formulations for the controlled release of these compounds . This work describes the conjugation of salicylic acid to a glycerol, AA HBPE, and its timed release from the HBPE conjugate through enzyme‐catalyzed hydrolytic degradation.…”

Degradable polyprodrugs: design and therapeutic efficiency

“…24c). 169 Polymerizing of HBA at 170 °C yielded the production of polyesters instead of poly(anhydride–ester)s by thermal rearrangement, confirming that lower temperatures are suitable for this reaction.…”

“…With the aim of simplifying the preparation of the polyprodrug, a one-step reaction was performed by reacting salicylic acid with adipoyl chloride in pyridine, followed without purification, by the conversion of diacids to mixed dianhydrides after a reaction with acetic anhydride. 169 By removing the pyridine and the excess of acetic anhydride and by proceeding the melt polycondensation at 175 °C, a poly(anhydride–ester) with a molecular weight of 22 700 g mol −1 was obtained.…”

Hyperbranched Poly (Ester)S from renewable Bio Monomers by Design: Nontoxic Platforms for the delivery of therapeutic agents

“…A glycerol/succinic acid hyperbranched poly(ester) may also be used for the preparation of similar prodrugs. Salicylic acid is a common therapeutic used for the treatment of acne and inflammation [13][14][15]. Controlled release of the active agent from the drug/polymer conjugate would enhance the duration of effectiveness while minimizing skin irritation.…”