Thermosensitive Hydrogel Based on Poly(2-Ethyl-2-Oxazoline)–Poly(D,L-Lactide)–Poly(2-Ethyl-2-Oxazoline) for Sustained Salmon Calcitonin Delivery

• DOI: 10.1208/s12249-020-1619-1
• Publication Date: 2020-01-17T17:03:01Z
• Authors: Xiaoning Wang; Yang Wang; Mengru Yan; Xiaoyan Liang; Ning Zhao; Yuantao Ma; Yingchun Gao
• Keywords: Calcitonin; Male; Bone Density Conservation Agents; Polymers; Drug Compounding; Polyesters; Temperature; Hydrogels; 02 engineering and technology; Rats; 12. Responsible consumption; Rats, Sprague-Dawley; Mice; Delayed-Action Preparations; Microscopy, Electron, Scanning; Polyamines; Animals; Calcium; Rheology; 0210 nano-technology; Oxazoles

This study developed a thermosensitive hydrogel based on poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-poly(2-ethyl-2-oxazoline) (PPP) for the delivery of salmon calcitonin to improve the hypocalcemic effect. The tube inversion and rheological tests revealed that the copolymer solution underwent temperature-dependent sol-gel-sol transitions. Observation by scanning electron microscopy (SEM) showed that the hydrogel exhibited a porous three-dimensional network. The swelling test demonstrated that there was a maximum swelling ratio at low temperature (25°C) as compared with the high temperature (37°C). In vitro release revealed that the PPP hydrogel were capable of sustained release of salmon calcitonin (sCT). The in vivo biodegradability study indicated the good degradability of PPP hydrogel. More importantly, the in vivo retention time of the hydrogel in situ was significantly prolonged after subcutaneous injection of the PPP hydrogel compared to the F127 hydrogel. In vivo pharmacodynamics analysis showed that the hypocalcemic effect of both PPP and F127 hydrogel was significantly greater than that of sCT solution, and the mean serum Ca reduction effect could be maintained for 24 h of PPP hydrogel, indicating that PPP hydrogel could achieve a significant enhanced hypocalcemic effect. In conclusion, the PPP hydrogel has been shown to be prospective as a controlled release carrier for injection delivery of protein drugs.