Calcitonin-Loaded Thermosensitive Hydrogel for Long-Term Antiosteopenia Therapy

Abstract

Effective antiosteopenia therapy can be achieved by designing long-term protein/peptide drug delivery systems for bone trabecula restoration. Here we show that a complex of salmon calcitonin and oxidized calcium alginate (sCT-OCA) was prepared and loaded into a thermosensitive copolymer hydrogel for long-term antiosteopenia treatment. The triblock copolymer, poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) exhibited sol-gel transition at body temperature. The sustained release of sCT from the in situ gelling system was determined by both the degradation of the hydrogel and the decomposition of the sCT-OCA complex. This system showed sustained effects in reducing serum calcium and bone trabecula reconstruction in the treatment of glucocorticoid-induced osteopenia in rats for approximately 30 days after a single subcutaneous injection, which may shed light on antiosteopenia therapy in the future.

Controlled Delivery of Salmon Calcitonin Using Thermosensitive Triblock Copolymer Depot for Treatment of Osteoporosis

“…From this initial study, further testing using sCT was explored in this research using the insight gained. 45 Both lysozyme and sCT retained bioactivity as evidenced by CD, MALDI-TOF mass spectroscopy, and HPLC analysis of entrapped and released therapeutic, demonstrating the ability of the copolymer to protect the structure of sensitive protein and peptide-based therapeutics. Release of therapeutics was observed over the course of 28 and 42 days for lysozyme and sCT, respectively.…”

“…They found that in vivo in rats over 30 days that the treatment was effective in decreasing serum calcium and bone reconstruction while under glucocorticoid-induced osteopenia. 45 In addition, Li et al were able to investigate a supramolecular nanoparticle of a dipeptide (Asp–Phe, DF) that was complexed with sCT in vitro and in vivo. Release of over one month showed promise as a system that can bypass polymeric materials.…”

Atherosclerosis Treatment with Stimuli‐Responsive Nanoagents: Recent Advances and Future Perspectives

“…Nanogels can be one of the excellent candidates for SRNAGs. Nanogels or hydrogel nanoparticles have the ability to encapsulate different biologically active molecules such as drugs, proteins, and genes and can be programmed to release the cargo via different external stimuli, such as light, ultrasound, electric field, and magnetic field or internal stimuli, such as pH, temperature, enzymes, and redox potential …”

Structures and Applications of Thermoresponsive Hydrogels and Nanocomposite-Hydrogels Based on Copolymers with Poly (Ethylene Glycol) and Poly (Lactide-Co-Glycolide) Blocks

“…They prepared hCT-cucurbit 7 (CB7) complex (cucurbit 7 is an amphiphilic small molecule) to inhibit the fibrillation of highly amyloidogenic hCT by CB7, then incorporated the hCT-CB7 complex into PLGA-PEG-PLGA hydrogel. As another example, a delivery system for salmon calcitonin (sCT), a bioactive peptide to regulate serum calcium concentration by a therapeutic effect to improve bone mass and relieve osteoporotic bone pain, for long-term anti-osteopenia treatment was investigated by Liu et al [48]. They prepared a complex of sCT and oxidized calcium alginate (OCA), a negatively charged polyelectrolyte, to stabilize sCT and control its affinity, then incorporated the sCT-OCA complex into PLGA-PEG-PLGA hydrogels.…”