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Factors Controlling Drug Release in Cross-linked Poly(valerolactone) Based Matrices.
Le Devedec, Frantz; Boucher, Hilary; Dubins, David; Allen, Christine.
Afiliación
  • Le Devedec F; Leslie Dan Faculty of Pharmacy , University of Toronto , 44 College Street , Ontario M5S 3M2 , Canada.
  • Boucher H; Leslie Dan Faculty of Pharmacy , University of Toronto , 44 College Street , Ontario M5S 3M2 , Canada.
  • Dubins D; Leslie Dan Faculty of Pharmacy , University of Toronto , 44 College Street , Ontario M5S 3M2 , Canada.
  • Allen C; Leslie Dan Faculty of Pharmacy , University of Toronto , 44 College Street , Ontario M5S 3M2 , Canada.
Mol Pharm ; 15(4): 1565-1577, 2018 04 02.
Article en En | MEDLINE | ID: mdl-29433315
ABSTRACT
There is keen interest in the development of biocompatible and biodegradable implantable delivery systems (IDDS) that provide sustained drug release for prolonged periods in humans. These systems have the potential to enhance therapeutic outcomes, reduce systemic toxicity, and improve patient compliance. Herein, we report the preparation and physicochemical characterization of cross-linked polymeric matrices from poly(valerolactone)- co-poly(allyl-δ-valerolactone) (PVL- co-PAVL) copolymers for use in drug delivery. A series of well-defined PVL- co-PAVL copolymers (PDI < 1.5) that vary in terms of MW and AVL content were prepared by ring opening polymerization catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene. A subsequent cross-linking reaction using 1,6-hexanedithiol led to solid cylindrical amorphous or semicrystalline matrices as potential IDDS. High loading levels (up to 20% (w/w)) of several model drugs that vary in physicochemical properties, including paclitaxel, triamcinolone acetonide and hexacetonide, curcumin, and acetaminophen, were achieved using a postloading method in organic solvent. Drug-IDDS interactions were evaluated via the group contribution method and X-ray diffraction as well as calorimetric, spectroscopic, and microscopic techniques. Results indicate superior drug-matrix compatibility for drugs bearing phenyl groups. In vitro release studies under distinct sink conditions highlight the key factors (i.e., state and loading level of drug, solubility of drug in external media, and composition of release media) that impact drug release.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polímeros / Pironas / Liberación de Fármacos Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polímeros / Pironas / Liberación de Fármacos Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Pharm Asunto de la revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá