期刊
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
卷 23, 期 7, 页码 689-696出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10837450.2017.1315134
关键词
Drug solubilization; PAMAM dendrimers; PEGylation; Silybin; supramolecular complexation
资金
- Fondo Nacional de Desarrollo Cientifico y Tecnologico
PEGylated PAMAM-G4 dendrimers with substitution percentages of 50% and intermediate size PEG chains (0.55 and 2.0kDa) were synthesized and evaluated as solubility enhancers and potential supramolecular carriers for the poorly soluble drug Silybin (SIL). Aqueous solubility profiles revealed that the PEGylated system with 2.0kDa chains induced a five-fold solubility increase for SIL and the largest drug-loading capacity within the systems under study with an average complex stoichiometry of 71:1 according to the Higuchi-Connors formulation for multiple binding sites. The supramolecular interaction between SIL and PEGylated PAMAM-G4 dendrimers was confirmed by 2D-NOESY experiments, which evidenced the simultaneous complexation of the drug in both PAMAM-G4 branches and outermost PEG chains. In vitro release studies showed that 2.0kDa PEG chains induced a more extended release time compared with 0.5kDa PEG chains. This result was attributed to the enhancement of PEG assistance to SIL complexation in systems with longer PEG chains, which are able to self-penetrate into dendrimer cavities and cooperate in the stabilization of SIL complexes, thus delaying the release of SIL from the supramolecular host. These results are valuable for the future design and development of novel PAMAM-based systems for SIL complexation and delivery.
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