Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA

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Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA. / Howard, K A; Dash, P R; Read, M L; Ward, K; Tomkins, L M; Nazarova, O; Ulbrich, K; Seymour, L W.

In: Biochimica et Biophysica Acta, Vol. 1475, No. 3, 26.07.2000, p. 245-55.

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@article{02cbf5c829484ed28f1e41ea62d8cca0,
title = "Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA",
abstract = "To investigate the possibility of producing charge-neutral gene delivery complexes with extended, non-particulate structures, DNA was allowed to self-assemble with a series of hydrophilic cationic polymers containing quaternary charged trimethylammonio ethylmethacrylate (TMAEM, 5, 15, 50, 100 mol%) copolymerised with hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA, 95, 85, 50, 0 mol%, respectively). Copolymers were all able to bind DNA, assessed using ethidium bromide fluorescence, although copolymers with low TMAEM content did not expel ethidium bromide. Increasing TMAEM content of the copolymers changed the morphology of the complexes from extended (5-15 mol% TMAEM), through partially condensed particles (50 mol%) to discrete nanoparticles (100 mol% TMAEM). Complexes based on copolymers with low TMAEM content (5-50 mol%) showed less resistance to degradation by nucleases and lower surface charge (21.2+/-5.9-45.1+/-3.9 mV) than those formed using 100 mol% TMAEM (57.8+/-8.2 mV). They also showed significantly less association with phagocytic cells in vitro (human leucocytes, uptake decreased by up to 92.3%; murine peritoneal macrophages, uptake decreased by up to 69.6%), although in vivo their hepatic accumulation was only slightly decreased (maximum decrease 27.6%). Finding the appropriate balance of hydrophilicity and stability is key to development of effective vectors for gene delivery.",
keywords = "Animals, Cations, DNA, Endonucleases, Ethidium, Gene Transfer Techniques, Genetic Therapy, Humans, Leukocytes, Macrophages, Peritoneal, Methacrylates, Mice, Microscopy, Electron, Microscopy, Fluorescence, Phagocytosis, Polyamines, Polymers, Static Electricity",
author = "Howard, {K A} and Dash, {P R} and Read, {M L} and K Ward and Tomkins, {L M} and O Nazarova and K Ulbrich and Seymour, {L W}",
year = "2000",
month = jul,
day = "26",
language = "English",
volume = "1475",
pages = "245--55",
journal = "Biochimica et Biophysica Acta",
issn = "1874-9399",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA

AU - Howard, K A

AU - Dash, P R

AU - Read, M L

AU - Ward, K

AU - Tomkins, L M

AU - Nazarova, O

AU - Ulbrich, K

AU - Seymour, L W

PY - 2000/7/26

Y1 - 2000/7/26

N2 - To investigate the possibility of producing charge-neutral gene delivery complexes with extended, non-particulate structures, DNA was allowed to self-assemble with a series of hydrophilic cationic polymers containing quaternary charged trimethylammonio ethylmethacrylate (TMAEM, 5, 15, 50, 100 mol%) copolymerised with hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA, 95, 85, 50, 0 mol%, respectively). Copolymers were all able to bind DNA, assessed using ethidium bromide fluorescence, although copolymers with low TMAEM content did not expel ethidium bromide. Increasing TMAEM content of the copolymers changed the morphology of the complexes from extended (5-15 mol% TMAEM), through partially condensed particles (50 mol%) to discrete nanoparticles (100 mol% TMAEM). Complexes based on copolymers with low TMAEM content (5-50 mol%) showed less resistance to degradation by nucleases and lower surface charge (21.2+/-5.9-45.1+/-3.9 mV) than those formed using 100 mol% TMAEM (57.8+/-8.2 mV). They also showed significantly less association with phagocytic cells in vitro (human leucocytes, uptake decreased by up to 92.3%; murine peritoneal macrophages, uptake decreased by up to 69.6%), although in vivo their hepatic accumulation was only slightly decreased (maximum decrease 27.6%). Finding the appropriate balance of hydrophilicity and stability is key to development of effective vectors for gene delivery.

AB - To investigate the possibility of producing charge-neutral gene delivery complexes with extended, non-particulate structures, DNA was allowed to self-assemble with a series of hydrophilic cationic polymers containing quaternary charged trimethylammonio ethylmethacrylate (TMAEM, 5, 15, 50, 100 mol%) copolymerised with hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA, 95, 85, 50, 0 mol%, respectively). Copolymers were all able to bind DNA, assessed using ethidium bromide fluorescence, although copolymers with low TMAEM content did not expel ethidium bromide. Increasing TMAEM content of the copolymers changed the morphology of the complexes from extended (5-15 mol% TMAEM), through partially condensed particles (50 mol%) to discrete nanoparticles (100 mol% TMAEM). Complexes based on copolymers with low TMAEM content (5-50 mol%) showed less resistance to degradation by nucleases and lower surface charge (21.2+/-5.9-45.1+/-3.9 mV) than those formed using 100 mol% TMAEM (57.8+/-8.2 mV). They also showed significantly less association with phagocytic cells in vitro (human leucocytes, uptake decreased by up to 92.3%; murine peritoneal macrophages, uptake decreased by up to 69.6%), although in vivo their hepatic accumulation was only slightly decreased (maximum decrease 27.6%). Finding the appropriate balance of hydrophilicity and stability is key to development of effective vectors for gene delivery.

KW - Animals

KW - Cations

KW - DNA

KW - Endonucleases

KW - Ethidium

KW - Gene Transfer Techniques

KW - Genetic Therapy

KW - Humans

KW - Leukocytes

KW - Macrophages, Peritoneal

KW - Methacrylates

KW - Mice

KW - Microscopy, Electron

KW - Microscopy, Fluorescence

KW - Phagocytosis

KW - Polyamines

KW - Polymers

KW - Static Electricity

M3 - Article

C2 - 10913823

VL - 1475

SP - 245

EP - 255

JO - Biochimica et Biophysica Acta

JF - Biochimica et Biophysica Acta

SN - 1874-9399

IS - 3

ER -