title: Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.
abstract: We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers.
authors.affiliation: Canada Research Chair on Bio-inspired Materials and Interfaces, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada; Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rabanel
authors.affiliation: Canada Research Chair on Bio-inspired Materials and Interfaces, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Faivre
authors.affiliation: INRS-Institut Armand-Frappier, 531, Boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Ghislain Djiokeng
authors.initials: GD
authors.lastname: Paka
authors.affiliation: INRS-Institut Armand-Frappier, 531, Boulevard des Prairies, Laval, Québec H7V 1B7, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
authors.affiliation: Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
authors.forename: Patrice
authors.initials: P
authors.lastname: Hildgen
authors.affiliation: Canada Research Chair on Bio-inspired Materials and Interfaces, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada. Electronic address: xavier.banquy@umontreal.ca.
authors.forename: Xavier
authors.initials: X
authors.lastname: Banquy
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D055592:Biophysical Phenomena / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy; D003474:Curcumin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D004058:Diffusion; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000009:adverse effects; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D007773:Lactates / Q000009:adverse effects / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000975:Antioxidants; D007773:Lactates; D018696:Neuroprotective Agents; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D003474:Curcumin
keywords: CNS; Comb-polymer; Curcumin; Micelle-like; Nanoaggregate; Nanoparticle; Poly(ethylene glycol); Poly(lactic); ROS; Toxicity