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This work aimed to achieve long-lasting delivery of radix ophiopogonis polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the ‘90%SAIB/10% solvent’ system was used, the mean residence time (MRT) of ROP was prolonged by 4.3 5 ∼ 7.00 times and the initial release rate was reduced significantly. However, this system was only suitable for days-long sustained release of ROP in short-term therapy. As to the ‘SAIB/additives/solvent’ system containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide-co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to months-long (16–60 d) smooth release of ROP could be achieved by varying the concentration (10–30%) and molecular weight (MW) of PLGA (10–50 kDa) or by employing a moderate MW of PEGylated ROP (∼20 or ∼30 kDa). With further increasing the conjugate MW to ∼40 kDa, the contribution of drug elimination to its plasma retention seemed to surpass that of the SAIB-based system, resulting in that the system no longer had an obvious influence on the in vivo behavior of the conjugate. Besides, the results of host response confirmed that with less solvent being used, the SAIB-based systems showed a higher biocompatibility than the PLGA-based systems, suggesting that they could be freely chosen in the prevention and/or cure of chronic diseases.

The herb Radix Ophiopogonis (RO) has been used effectively to treat nasopharyngeal carcinoma (NPC) as an adjunctive therapy. Due to the complexity of the traditional Chinese herbs, the pharmacological mechanism of RO’s action on NPC remains unclear. To address this problem, an integrative approach bridging proteome experiments with bioinformatics prediction was employed. First, differentially expressed protein profile from NPC serum samples was established using isobaric tag for relative and absolute quantification (iTRAQ) coupled 2-D liquid chromatography (LC)-MS/MS analysis. Second, the RO putative targets were predicted using Traditional Chinese Medicines Integrated Database and known therapeutic targets of NPC were collected from Drugbank and OMIM databases. Then, a network between RO putative targets and NPC known therapeutic targets was constructed. Third, based on pathways enrichment analysis, an integrative network was constructed using DAVID and STRING database in order to identify potential candidate targets of RO against NPC. As a result, we identified 13 differentially expressed proteins from clinical experiments compared with the healthy control. And by bioinformatics investigation, 12 putative targets of RO were selected. Upon interactions between experimental and predicted candidate targets, we identified three key candidate targets of RO against NPC: VEGFA, TP53, and HSPA8, by calculating the nodes’ topological features. In conclusion, this integrative pharmacology-based analysis revealed the anti-NPC effects of RO might be related to its regulatory impact via the PI3K-AKT signaling pathway, the Wnt signaling pathway, and the cAMP signaling pathway by targeting VEGFA, TP53, and HSPA8. The findings of potential key targets may provide new clues for NPC’s treatments with the RO adjunctive therapy.

The herb Radix Ophiopogonis (RO) has been used effectively to treat nasopharyngeal carcinoma (NPC) as an adjunctive therapy. Due to the complexity of the traditional Chinese herbs, the pharmacological mechanism of RO's action on NPC remains unclear. To address this problem, an integrative approach bridging proteome experiments with bioinformatics prediction was employed. First, differentially expressed protein profile from NPC serum samples was established using isobaric tag for relative and absolute quantification (iTRAQ) coupled 2-D liquid chromatography (LC)-MS/MS analysis. Second, the RO putative targets were predicted using Traditional Chinese Medicines Integrated Database and known therapeutic targets of NPC were collected from Drugbank and OMIM databases. Then, a network between RO putative targets and NPC known therapeutic targets was constructed. Third, based on pathways enrichment analysis, an integrative network was constructed using DAVID and STRING database in order to identify potential candidate targets of RO against NPC. As a result, we identified 13 differentially expressed proteins from clinical experiments compared with the healthy control. And by bioinformatics investigation, 12 putative targets of RO were selected. Upon interactions between experimental and predicted candidate targets, we identified three key candidate targets of RO against NPC: VEGFA, TP53, and HSPA8, by calculating the nodes' topological features. In conclusion, this integrative pharmacology-based analysis revealed the anti-NPC effects of RO might be related to its regulatory impact via the PI3K-AKT signaling pathway, the Wnt signaling pathway, and the cAMP signaling pathway by targeting VEGFA, TP53, and HSPA8. The findings of potential key targets may provide new clues for NPC's treatments with the RO adjunctive therapy. [ABSTRACT FROM AUTHOR]

This work aimed to achieve long-lasting delivery of radix ophiopogonis polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the '90%SAIB/10% solvent' system was used, the mean residence time (MRT) of ROP was prolonged by 4.3 5 ∼ 7.00 times and the initial release rate was reduced significantly. However, this system was only suitable for days-long sustained release of ROP in short-term therapy. As to the 'SAIB/additives/solvent' system containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide-co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to months-long (16-60 d) smooth release of ROP could be achieved by varying the concentration (10-30%) and molecular weight (MW) of PLGA (10-50 kDa) or by employing a moderate MW of PEGylated ROP (∼20 or ∼30 kDa). With further increasing the conjugate MW to ∼40 kDa, the contribution of drug elimination to its plasma retention seemed to surpass that of the SAIB-based system, resulting in that the system no longer had an obvious influence on the in vivo behavior of the conjugate. Besides, the results of host response confirmed that with less solvent being used, the SAIB-based systems showed a higher biocompatibility than the PLGA-based systems, suggesting that they could be freely chosen in the prevention and/or cure of chronic diseases. [ABSTRACT FROM AUTHOR]