title: Improving paclitaxel delivery: in vitro and in vivo characterization of PEGylated polyphosphoester-based nanocarriers.
abstract: Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to <2.0 μg/mL for the aqueous solubility of the drug alone. Drug release studies indicated that PTX released from these nanostructures was defined through a structure-function relationship, whereby the half-life of sustained PTX release was doubled through cross-linking of the micellar structure to form SCKs. In vitro, physically loaded micellar and SCK nanotherapeutics demonstrated IC50 values against osteosarcoma cell lines, known to metastasize to the lungs (CCH-OS-O and SJSA), similar to the pharmaceutical Taxol formulation. Evaluation of these materials in vivo has provided an understanding of the effects of nanoparticle structure-function relationships on intratracheal delivery and related biodistribution and pharmacokinetics. Overall, we have demonstrated the potential of these novel nanotherapeutics toward future sustained release treatments via administration directly to the sites of lung metastases of osteosarcoma.
authors: Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, ‡Laboratory for Synthetic-Biologic Interactions, and §Texas A&M Institute for Preclinical Studies, Texas A&M University , College Station, Texas 77842, United States.
authors: Fuwu
authors: F
authors: Zhang
authors: Shiyi
authors: S
authors: Zhang
authors: Stephanie F
authors: SF
authors: Pollack
authors: Richen
authors: R
authors: Li
authors: Amelia M
authors: AM
authors: Gonzalez
authors: Jingwei
authors: J
authors: Fan
authors: Jiong
authors: J
authors: Zou
authors: Sarah E
authors: SE
authors: Leininger
authors: Adriana
authors: A
authors: Pavía-Sanders
authors: Rachel
authors: R
authors: Johnson
authors: Laura D
authors: LD
authors: Nelson
authors: Jeffery E
authors: JE
authors: Raymond
authors: Mahmoud
authors: M
authors: Elsabahy
authors: Dennis M P
authors: DM
authors: Hughes
authors: Mark W
authors: MW
authors: Lenox
authors: Tiffany P
authors: TP
authors: Gustafson
authors: Karen L
authors: KL
authors: Wooley
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry; D001859:Bone Neoplasms / Q000473:pathology; D002384:Catalysis; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D065546:Drug Liberation; D004952:Esters; D006207:Half-Life; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D012516:Osteosarcoma / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000480:Alkynes; D001386:Azides; D004337:Drug Carriers; D004952:Esters; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D003300:Copper; D017239:Paclitaxel