Optimization and evaluation of astragalus polysaccharide injectable thermoresponsive in-situ gels

The objective of this study was to develop an injectable in situ forming gel system based on Poloxamer for sustained release of Astragalus polysaccharide (APS), thus achieved once or twice administration instead of frequent dosing during long-term treatment. The optimal formulation is 10 g APS, 18 g poloxamer 407, 2 g poloxamer 188, 0.15 g CMC-Na, 0.85 g sodium chloride in 100 ml gel in situ which had a preferable sol-gel transition temperature(T sol-gel) (34.1 +/- 0.4 degrees C), and good stability. In vitro release studies, all formulations containing polymer additives had prolonged release time and decreased initial burst to some extent. The optimal formulation containing 0.15% CMC-Na showed a best sustained release profile for about 132 h with the lowest initial burst in vitro about 16.30% in 12 h). In vivo, Male BALB/c mice (18 - 20 g) were administrated with APS in-situ gel just once, the values of immune organ indices, spleen lymphocyte proliferation, and serum IgM, IgG, IL-2 and IL-6 had significant increase, which was consistent with the mice given daily APS injections (7 times), while the above indices were increased more significantly in which administrated with APS in-situ gel twice. Based on these results, it can be concluded that the Poloxamer depot is a promising carrier for the sustained release of APS with an ideal release behavior.