title: Sulfated glycosaminoglycan-based block copolymer: preparation of biocompatible chondroitin sulfate-b-poly(lactic acid) micelles.
abstract: Despite a growing interest in amphiphilic polysaccharide-based diblock copolymers as functional polymeric drug delivery nanosystems, biologically relevant sulfated glycosaminoglycan systems were not yet investigated. Here, we report the synthesis and the self-assembly properties in water of chondroitin sulfate-b-poly(lactic acid) (CS-b-PLA(n)). The CS-b-PLA(n) were synthesized using click-grafting onto method implying reducing-end alkynation of low-molecular weight depolymerized CS (M(w) = 5000 g·mol(-1)) and azide-terminated functionalization of PLAn (M(w) = 6500 g·mol(-1) (n = 46) and M(w) = 1700 g·mol(-1) (n = 20)). The diblock copolymer self-assembled in water giving rise to spherical micelles that were characterized in solution using dynamic/static light scattering and at dry state by TEM technique. In vitro assays on healthy cells showed that at high concentrations, up to 10 μg·mL(-1), CS-b-PLA(n) were noncytotoxic. Those preliminary studies are promising in the perspective to use them as biocompatible nanovehicles for anticancer drug delivery.
authors.affiliation: Centre de Recherches sur les Macromolécules Végétales (CERMAV, UPR-CNRS 5301), Université Grenoble Alpes , BP 53, 38041 Grenoble Cedex 9, France.
authors.forename: André R
authors.initials: AR
authors.lastname: Fajardo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guerry
authors.forename: Elizandra A
authors.initials: EA
authors.lastname: Britta
authors.forename: Celso V
authors.initials: CV
authors.lastname: Nakamura
authors.forename: Edvani C
authors.initials: EC
authors.lastname: Muniz
authors.forename: Redouane
authors.initials: R
authors.lastname: Borsali
authors.forename: Sami
authors.initials: S
authors.lastname: Halila
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D057930:Click Chemistry; D003871:Dermatan Sulfate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000633:toxicity; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D003871:Dermatan Sulfate; D019344:Lactic Acid; C033616:poly(lactide)