title: Self-aggregation of cationically modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers: Effect of cationic grafting ligand and poly(ε-caprolactone) chain length.
abstract: Cationic copolymers have been attractive to investigate due to their potential to complexation with anionic drugs and expected to use in the pharmaceutical application. In this study, the modified poly(ε-caprolactone)2-co-poly(ethylene glycol) copolymers (P(CL)2-PEG) were successfully synthesized by click reaction. The amount of small molecular cationic ligand, propargyltrimethyl ammonium iodide, was varied and grafted onto various mole ratios of P(CL) to PEG. The effects of P(CL) chain length and amount of the grafting cationic ligand on physicochemical properties of polymers and particles were studied. The number-average molecular weights of the copolymers grafted with cationic ligand were found ranging between 10,000 and 23,000g/mol as investigated by NMR. From DSC study, the results showed that the grafting ligand affected thermal behaviors of the copolymers by increasing the glass transition temperature and decreasing the melting temperature of the copolymers. Furthermore, these cationic copolymers could self-aggregate with their critical aggregation concentration depending on mole ratios of hydrophilic to hydrophobic portions. The particles containing higher amounts of the cationic ligand tended to aggregate in both acidic and basic pH environment and at high salt concentration. Additionally, particle size, size distribution (PdI), and morphology of self-assembling particles varied depending on P(CL) chain length and the amount of the grafting cationic ligand. The synthesized cationic copolymer showed a capability to encapsulate a high negatively charged drug, enoxaparin, with an encapsulation efficiency of 87%. After drug incorporation, the particles substantially changed in size, shape, PdI, and zeta potential to become more suitable for drug delivery. These cationic copolymers with flexible properties will be the candidate for further development as carriers for the delivery of negatively charged drugs.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Pimchanok
authors.initials: P
authors.lastname: Charoongchit
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Jiraphong
authors.initials: J
authors.lastname: Suksiriworapong
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Kittisak
authors.initials: K
authors.lastname: Sripha
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy 54001, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sapin-Minet
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy 54001, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand. Electronic address: varaporn.jun@mahidol.ac.th.
authors.forename: Varaporn Buraphacheep
authors.initials: VB
authors.lastname: Junyaprasert
mesh_terms: D002152:Calorimetry, Differential Scanning; D002412:Cations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D009994:Osmolar Concentration; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
chemical_list: D002412:Cations; D004337:Drug Carriers; D008024:Ligands; D004364:Pharmaceutical Preparations; D011091:Polyesters; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); C016240:polycaprolactone; D011092:Polyethylene Glycols
keywords: Cationic copolymer; Click chemistry; Particle properties; Poly(ε-caprolactone)-co-poly(ethylene glycol); Self-aggregation