title: Partially PEGylated PAMAM dendrimers as solubility enhancers of Silybin.
abstract: PEGylated PAMAM-G4 dendrimers with substitution percentages of 50% and intermediate size PEG chains (0.55 and 2.0 kDa) 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 2.0 kDa 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 2.0 kDa PEG chains induced a more extended release time compared with 0.5 kDa 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.
authors.affiliation: a Departamento de Química Orgánica, Facultad de Ciencias Químicas , Universidad de Concepción , Concepción , Chile.
authors.forename: Carola
authors.initials: C
authors.lastname: Diaz
authors.affiliation: b Departamento de Fisiología, Facultad de Ciencias Biológicas , Universidad de Concepción , Concepción , Chile.
authors.forename: José
authors.initials: J
authors.lastname: Guzmán
authors.affiliation: c Departamento de Ciencias Químicas, Facultad de Ciencias Exactas , Universidad Andrés Bello, Sede Concepción , Talcahuano , Chile.
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Jiménez
authors.affiliation: a Departamento de Química Orgánica, Facultad de Ciencias Químicas , Universidad de Concepción , Concepción , Chile.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Alderete
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D057809:HEK293 Cells; D006801:Humans; D009757:Nylons / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility
chemical_list: D000975:Antioxidants; D050091:Dendrimers; D004337:Drug Carriers; D009757:Nylons; C520550:PAMAM-G4; D012838:Silymarin; D011092:Polyethylene Glycols; D000077385:Silybin
keywords: Drug solubilization; PAMAM dendrimers; PEGylation; Silybin; supramolecular complexation