Tags

Type your tag names separated by a space and hit enter

Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate).
Colloids Surf B Biointerfaces 2018; 167:115-125CS

Abstract

Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5-9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates.

Authors+Show Affiliations

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Ratchathewi, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand. Electronic address: jiraphong.suk@mahidol.ac.th.University of Nottingham, School of Pharmacy, University Park, Nottingham, NG7 2RD, UK.Division of Cancer and Stem Cells, Cancer Biology, University of Nottingham, Nottingham, NG7 2RD, UK.University of Nottingham, School of Pharmacy, University Park, Nottingham, NG7 2RD, UK.Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand.Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Ratchathewi, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand.University of Nottingham, School of Pharmacy, University Park, Nottingham, NG7 2RD, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29631222

Citation

Suksiriworapong, Jiraphong, et al. "Synthesis and Properties of a Biodegradable Polymer-drug Conjugate: Methotrexate-poly(glycerol Adipate)." Colloids and Surfaces. B, Biointerfaces, vol. 167, 2018, pp. 115-125.
Suksiriworapong J, Taresco V, Ivanov DP, et al. Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate). Colloids Surf B Biointerfaces. 2018;167:115-125.
Suksiriworapong, J., Taresco, V., Ivanov, D. P., Styliari, I. D., Sakchaisri, K., Junyaprasert, V. B., & Garnett, M. C. (2018). Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate). Colloids and Surfaces. B, Biointerfaces, 167, pp. 115-125. doi:10.1016/j.colsurfb.2018.03.048.
Suksiriworapong J, et al. Synthesis and Properties of a Biodegradable Polymer-drug Conjugate: Methotrexate-poly(glycerol Adipate). Colloids Surf B Biointerfaces. 2018 Jul 1;167:115-125. PubMed PMID: 29631222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate). AU - Suksiriworapong,Jiraphong, AU - Taresco,Vincenzo, AU - Ivanov,Delyan P, AU - Styliari,Ioanna D, AU - Sakchaisri,Krisada, AU - Junyaprasert,Varaporn Buraphacheep, AU - Garnett,Martin C, Y1 - 2018/03/28/ PY - 2017/12/06/received PY - 2018/03/10/revised PY - 2018/03/27/accepted PY - 2018/4/10/pubmed PY - 2018/10/3/medline PY - 2018/4/10/entrez KW - Methotrexate KW - Nanoparticle KW - Osteosarcoma cell KW - Poly(glycerol adipate) KW - Polymer-drug conjugate SP - 115 EP - 125 JF - Colloids and surfaces. B, Biointerfaces JO - Colloids Surf B Biointerfaces VL - 167 N2 - Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5-9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates. SN - 1873-4367 UR - https://www.unboundmedicine.com/medline/citation/29631222/Synthesis_and_properties_of_a_biodegradable_polymer_drug_conjugate:_Methotrexate_poly_glycerol_adipate__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0927-7765(18)30198-X DB - PRIME DP - Unbound Medicine ER -