Supramolecular gels of poly-α-cyclodextrin and PEO-based copolymers for controlled drug release.
The aim of this work was to prepare syringeable supramolecular gels of α-cyclodextrin-polymer (poly-αCD) with various poly(ethylene oxide) (PEO)-based copolymers, which can be suitable to form depots for controlled drug release. A series of water-soluble poly-αCDs was synthesized from αCD by crosslinking with epichlorohydrin in alkaline medium. The chemical composition of the polymers was characterized by NMR (αCD content>53%) and the molecular weight was evaluated using static light scattering (SLS). Supramolecular assemblies occurred by mixing poly-αCD (20-40% w/v) with a PEO-based polymer (i.e., PEG, Pluronic® F127 or Tetronic® 908) (10-15% w/v). Phase separation was observed and the αCD content in each phase was determined by means of the phenol-sulfuric acid colorimetric method. Formation of poly-αCD/PEO-based polymer 3D-supramolecular complexes was confirmed by diffusion-ordered NMR spectroscopy (DOSY) and X-ray diffractometry. The supramolecular assemblies showed good cytocompatibility against SAOS-2 cells and in the HET-CAM test. The supramolecular gels were able to sustain the release of vancomycin for at least 5 days at 37 °C, more efficiently than dispersions of each polymer component in separate. These results open new possibilities in the design of novel controlled delivery systems for the treatment of bone infections.
Department of Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Susana M N
SM
Simões
Department of Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Francisco
F
Veiga
Department of Chemistry, University of Coimbra, Coimbra, Portugal.
Ana C F
AC
Ribeiro
Department of Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Ana R
AR
Figueiras
Departamento de Física de la Materia Condensada, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Pablo
P
Taboada
Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
Angel
A
Concheiro
Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: Carmen.alvarez.lorenzo@usc.es.
Carmen
C
Alvarez-Lorenzo
D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004811:Epichlorohydrin / Q000008:administration & dosage / Q000737:chemistry; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008970:Molecular Weight; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D014640:Vancomycin / Q000008:administration & dosage / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*
D003692:Delayed-Action Preparations; D005782:Gels; C116176:PEO-PPO-PEO; D011108:Polymers; D011409:Propylene Glycols; D047391:alpha-Cyclodextrins; D004811:Epichlorohydrin; D020442:Poloxamer; D011092:Polyethylene Glycols; D014640:Vancomycin; C032613:alpha-cyclodextrin
Controlled drug release; Cyclodextrin polymer; Drug delivery; Polypseudorotaxane; Syringeable supramolecular gel; Vancomycin