Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small pept...Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin(TP5). To this end, implantable sandwich poly(hydroxybutyrate-co-hydroxyhexanoate)(PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4^+/CD8^+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.展开更多
基金supported by the National Natural Science Foundation of China(No.81673362)
文摘Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin(TP5). To this end, implantable sandwich poly(hydroxybutyrate-co-hydroxyhexanoate)(PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4^+/CD8^+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.
