ABSTRACT
Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.
ABSTRACT
@#Ophthalmic solution of organic-inorganic layered double hydroxides hybrid nanocomposites based on layered double hydroxides(LDH)intercalated with pirenoxine sodium(PRN)and chitosan-glutathione(CG)was prepared, characterized and evaluated using rabbit precorneal retention. Mg-Al-PRN-LDH, Zn-Al-PRN-LDH and CG-PRN-LDH were synthesized by co-precipitation. The nanocomposites were characterized by laser particle sizer, powder X-ray diffraction(X-RD), fourier transform infrared spectra(FTIR)and transmission electron micrographs(TEM). The release of PRN from Mg-Al-PRN-LDH, Zn-Al-PRN-LDH, and CG-PRN-LDH nanocomposites and API in artificial tear was compared. Based on in vivo precorneal retention studies, PRN-LDH and CG-PRN-LDH nanocomposite dispersions showed significantly higher AUC(3. 72-, 7. 59-folds)and MRT(2. 18-, 2. 60-folds)than that of the commercial eye drops group. Organic-inorganic layered double hydroxides hybrid nanocomposites CG-PRN-LDH dispersions could remarkably improve precorneal retention of PRN.