Pamidronate-Conjugated Biodegradable Branched Copolyester Carriers: Synthesis and Characterization

Abstract

The need for development of comprehensive therapeutic systems, (e.g., polymer-apatite composites) as a bone substitute material has previously been highlighted in many scientific reports. The aim of this study was to develop a new multifunctional composite based on hydroxyapatite porous granules doped with selenite ions (SeO32−) and a biodegradable branched copolymer-bisphosphonate conjugate as a promising bone substitute material for patients with bone tumours or bone metastasis. A series of biodegradable and branched copolymer matrices, adequate for delivery of bisphosphonate in the bone-deficient area were synthesized and physico-chemically and biologically (cyto- and genotoxicity assays) characterized. Branched copolymers were obtained using a hyperbranched bis-MPA polyester-16-hydroxyl initiator and Sn(Oct)2, a (co)catalyst of the ring-opening polymerization (ROP) of l,l-lactide (LLA) and ε-caprolactone (CL). A new amide bond was formed between the hydroxyl end groups of the synthesized copolymer carriers and an amine group of pamidronate (PAM)—the drug inhibiting bone resorption and osteoclast activity in bone. The dependence of the physico-chemical properties of the copolymer matrices on the kinetic release of PAM from the synthesized branched copolymer conjugate-coated hydroxyapatite granules doped with selenite ions was observed. Moreover, the correlation of these results with the hydrolytic degradation data of the synthesized matrices was evidenced. Therefore, the developed composite porous hydroxyapatite doped with SeO32− ions/biodegradable copolymer-PAM conjugate appears most attractive as a bone substitute material for cancer patients.

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications

“…Kido et al [86] used the Comet assay as a final assessment for genotoxicity on tissue samples obtained from rats that were exposed to a ceramic scaffold covered with HA and bioglass; their assays demonstrated the lack of genotoxic effects of the investigated material. Oledzka et al [87] investigated the cyto- and geno-toxicity of a new multifunctional composite based on HA porous granules doped with selenite ions (SeO 3 ) 2− , and their study proved that the investigated materials were non-gentotoxic, as demonstrated by the Umu test (carried out on S. typhimurium TA1535/pSK1002). Yamamura et al used in vivo models for the investigation of biocompatibility, and the lack of cyto- and geno-toxicity in blood, liver, kidney, and lung was noted 30 days after HA implantation [88].…”

“…Several studies [86,87,88] generally demonstrated, using various models, the lack of genotoxicity of HA-based materials.…”

How Accurate Is Oral Implant Installation Using Surgical Guides Printed from a Degradable and Steam-Sterilized Biopolymer?

“…Among other filaments, FDM technology allows for additive manufacturing of biopolymers such as lignin and polylactides (PLA), a biodegradable filament used for tissue engineering purposes in various fields of regenerative medicine and dentistry [24][25][26]. Despite environmental advantage in terms of biodegradability, recent studies showed improvements of the mechanical properties by changing the layups of the fibers of subsequent layers [20].…”

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

“…For example, ZOL-loaded bone cement or tricalcium phosphate (TCP) inhibited malignant bone tumors or metastatic bone tumors with the help of sustained ZOL release and acted as a bone substitute at the same time (Koto et al, 2017;Rahmanian et al, 2017). Aliphatic polyesters like PCL, PLA, PLLA were used widely for their good biodegradability, biocompatibility, and permeability (Oledzka et al, 2017). Ewa Oledzka et al prepared a new multifunctional composite as a promising bone substitute material in which HA porous granules doped with selenite ions (SeO 3 2À ) and conjugated biodegradable branched copolymer-BP.…”