title: Comparison of poly(ε-caprolactone) chain lengths of poly(ε-caprolactone)-co-d-α-tocopheryl-poly(ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells.
abstract: This study aimed to investigate the effect of the different hydrophobic chain lengths of poly(ε-caprolactone)-co-d-α-tocopheryl polyethylene glycol 1000 succinate (P(CL)-TPGS) copolymers on the nanoparticle properties and delivery efficiency of quercetin to SKBR3 breast cancer cells. The 5:1, 10:1 and 20:1 P(CL)-TPGS copolymers were fabricated and found to be composed of 25.0%, 45.2% and 66.8% of hydrophobic P(CL) chains with respect to the polymer chain, respectively. The DSC measurement indicated the microphase separation of P(CL) and TPGS segments. The crystallization of P(CL) segment occurred when the P(CL) chain was higher than 25% due to the restricted mobility of P(CL) by TPGS. The longer P(CL) chain had the higher crystallinity while decreasing the crystallinity of TPGS segment. The increasing P(CL) chain length increased the particle size of P(CL)-TPGS nanoparticles from 20 to 205 nm and enhanced the loading capacity of quercetin due to the more hydrophobicity of the nanoparticle core. The release of quercetin was retarded by an increase in P(CL) chain length associated with the increasing hydrophobicity and crystallinity of P(CL)-TPGS copolymers. The P(CL)-TPGS nanoparticles potentiated the toxicity of quercetin to SKBR3 cells by at least 2.9 times compared to the quercetin solution. The cellular uptake of P(CL)-TPGS nanoparticles by SKBR3 cells occurred through cholesterol-dependent endocytosis. The 10:1 P(CL)-TPGS nanoparticles showed the highest toxicity and uptake efficiency and could be potentially used for the delivery of quercetin to breast cancer cells.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand. Electronic address: jiraphong.suk@mahidol.ac.th.
authors.forename: Jiraphong
authors.initials: J
authors.lastname: Suksiriworapong
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Kittisak
authors.initials: K
authors.lastname: Phoca
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Supakanda
authors.initials: S
authors.lastname: Ngamsom
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Kittisak
authors.initials: K
authors.lastname: Sripha
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Primchanien
authors.initials: P
authors.lastname: Moongkarndi
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Varaporn Buraphacheep
authors.initials: VB
authors.lastname: Junyaprasert
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011794:Quercetin / Q000008:administration & dosage / Q000737:chemistry*; D013386:Succinates / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011091:Polyesters; D013386:Succinates; D014810:Vitamin E; C016240:polycaprolactone; D011092:Polyethylene Glycols; D011794:Quercetin; C014225:tocophersolan
keywords: Amiloride hydrochloride hydrate (PubChem CID: 23581809); Caprolactone (PubChem CID: 10401); Chlorpromazine hydrochloride (PubChem CID: 6240); Filipin III (PubChem CID: 5351457); Hydrophobic chain length; Nanoparticles; Poloxamer 407 (PubChem CID: 24751); Poly(ε-caprolactone); Quercetin; Quercetin (PubChem CID: 5280343); TPGS (PubChem CID: 71406); d-α-Tocopheryl polyethylene glycol 1000 succinate; β-Cyclodextrin (PubChem CID: 6518168)