Preparation and Evaluation of rhINF-α-2b Sodium Hyaluronate Cross-Linked Porous Microspheres: Characterization, Sustained-Release Properties, and Antitumor Activity

Recombinant human interferon alpha-2b (rhINF-alpha-2b), like most proteins, has several shortcomings such as relatively short half-life, low therapeutic index, high circulating drug fluctuations, and rapid degradation which could hinder its effective delivery. Novel electrostatic spray and ion exchange drug-loading techniques were combined to formulate rhINF-alpha-2b sodium hyaluronate cross-linked porous sustained-release microspheres (rhINF-alpha-2b-SHCPM), a protein delivery system. The different properties of rhINF-alpha-2b-SHCPM including the physicochemical nature, in vitro release behavior, and antitumor activity were evaluated. The loading rate (1031 +/- 0.94%) and encapsulation efficiency (89.09 +/- 237%) of rhINF-alpha-2b-SHCPM produced acceptable values. The in vitro cumulative release rate of rhINF-alpha-2b-SHCPM within 24 h was also 86.26 +/- 2.11% with a much better sustained release effect. Thus, the half-life (10.763 h) and retention time (14.067 h) of rhIFN alpha-2b-SHCPM were significantly prolonged with enhanced bioavailability (43,198.387 ng/L*h) and decreased peak concentration (15,266.4 ngL(-1)) compared with the free rhIFN alpha-2b protein (0.912 h, 0.952 h, 34,749.048 ng/L*h, and 48,870.2 ngL(-1), respectively). The in vitroanti-proliferative activity and in vivo tumor inhibitory rate of rhIFN alpha-2b-SHCPM also increased by 90 and 55.86%, respectively, compared with the free rhIFN alpha-2b solution. The findings significantly supported a well-developed protein delivery system with improved sustained release, acceptable bioavailability, and increased antitumor activities.