PH triggered release of protective poly(ethylene glycol)-b-polycation copolymers from liposomes

Debra T. Auguste; Steven P. Armes; Krystyna R. Brzezinska; Timothy J. Deming; Joachim Kohn; Robert K. Prud'homme

doi:10.1016/j.biomaterials.2005.08.036

PH triggered release of protective poly(ethylene glycol)-b-polycation copolymers from liposomes

Debra T. Auguste, Steven P. Armes, Krystyna R. Brzezinska, Timothy J. Deming, Joachim Kohn, Robert K. Prud'homme

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

Triggered release of adsorbed polymers from liposomes enables protection against immune recognition during circulation and subsequent intracellular delivery of DNA. Polycationic blocks, poly[2-(dimethylamino) ethyl methacrylate] (DMAEMA) (0.8, 3.1, 4.9, or 9.8 kg/mol) or polylysine (K) (3 kg/mol), act as anchors for poly(ethylene glycol) (PEG) (2 or 5 kg/mol) protective blocks. In addition, a copolymer with 15 strictly alternating blocks of PEG (2 kg/mol) and cationic amine sites was evaluated as a protective coating. Incorporation of 1,2-dioleoyl-3-dimethylammonium-propane, a titratable lipid with a pKa of ∼6.7, allows the liposome's net charge to increase as the pH shifts from 7.4 in the bloodstream to 5.5 in the endosome. The increased net liposome cationicity results in decreased cationic polymer adsorption. The EMPEG113-DMAEMA31 and EMPEG113-DMAEMA62 association constants decrease from 3.1 and 6.2 (mg/m²)/(mg/ml) at pH 7.4 to 1.7 and 3.2 (mg/m ²)/(mg/ml) at pH 5.5, respectively. However, EMPEG45-DMAEMA5, EMPEG45-DMAEMA20, and EMPEG45-N-DP15 did not show a strong response to changes in pH. Cationic polymer adsorption exceeds calculated values for liposome neutralization, resulting in adsorption profiles in the brush regime.

Original language	English (US)
Pages (from-to)	2599-2608
Number of pages	10
Journal	Biomaterials
Volume	27
Issue number	12
DOIs	https://doi.org/10.1016/j.biomaterials.2005.08.036
State	Published - Apr 2006

All Science Journal Classification (ASJC) codes

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

Keywords

Adsorption
Controlled drug release
Drug delivery
Gene therapy
Liposomes
Polyethylene oxide

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10.1016/j.biomaterials.2005.08.036

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@article{e33a4a59bc434173a1e32449a770756b,

title = "PH triggered release of protective poly(ethylene glycol)-b-polycation copolymers from liposomes",

abstract = "Triggered release of adsorbed polymers from liposomes enables protection against immune recognition during circulation and subsequent intracellular delivery of DNA. Polycationic blocks, poly[2-(dimethylamino) ethyl methacrylate] (DMAEMA) (0.8, 3.1, 4.9, or 9.8 kg/mol) or polylysine (K) (3 kg/mol), act as anchors for poly(ethylene glycol) (PEG) (2 or 5 kg/mol) protective blocks. In addition, a copolymer with 15 strictly alternating blocks of PEG (2 kg/mol) and cationic amine sites was evaluated as a protective coating. Incorporation of 1,2-dioleoyl-3-dimethylammonium-propane, a titratable lipid with a pKa of ∼6.7, allows the liposome's net charge to increase as the pH shifts from 7.4 in the bloodstream to 5.5 in the endosome. The increased net liposome cationicity results in decreased cationic polymer adsorption. The EMPEG113-DMAEMA31 and EMPEG113-DMAEMA62 association constants decrease from 3.1 and 6.2 (mg/m2)/(mg/ml) at pH 7.4 to 1.7 and 3.2 (mg/m 2)/(mg/ml) at pH 5.5, respectively. However, EMPEG45-DMAEMA5, EMPEG45-DMAEMA20, and EMPEG45-N-DP15 did not show a strong response to changes in pH. Cationic polymer adsorption exceeds calculated values for liposome neutralization, resulting in adsorption profiles in the brush regime.",

keywords = "Adsorption, Controlled drug release, Drug delivery, Gene therapy, Liposomes, Polyethylene oxide",

author = "Auguste, {Debra T.} and Armes, {Steven P.} and Brzezinska, {Krystyna R.} and Deming, {Timothy J.} and Joachim Kohn and Prud'homme, {Robert K.}",

note = "Funding Information: The authors would like to thank James Whitacre and Samuel Kahn who worked on the preliminary electrophoretic mobility measurements of charged liposomes. The authors would also like to thank Dr. Das Bolikal for synthesis of the electrostatically modified comb-graft copolymer (EMPEG45–N-DP15) and Dr. Maria Vamvakaki for synthesis of the EMPEG–DMAEMA diblock copolymers. In addition, the authors acknowledge funding from Elan Pharmaceuticals (formerly The Liposome Company) and the New Jersey Center for Biomaterials. D. Auguste acknowledges the 1930 Wallace Memorial fellowship from the Princeton University Graduate School. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2006",

month = apr,

doi = "10.1016/j.biomaterials.2005.08.036",

language = "English (US)",

volume = "27",

pages = "2599--2608",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "12",

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TY - JOUR

T1 - PH triggered release of protective poly(ethylene glycol)-b-polycation copolymers from liposomes

AU - Auguste, Debra T.

AU - Armes, Steven P.

AU - Brzezinska, Krystyna R.

AU - Deming, Timothy J.

AU - Kohn, Joachim

AU - Prud'homme, Robert K.

N1 - Funding Information: The authors would like to thank James Whitacre and Samuel Kahn who worked on the preliminary electrophoretic mobility measurements of charged liposomes. The authors would also like to thank Dr. Das Bolikal for synthesis of the electrostatically modified comb-graft copolymer (EMPEG45–N-DP15) and Dr. Maria Vamvakaki for synthesis of the EMPEG–DMAEMA diblock copolymers. In addition, the authors acknowledge funding from Elan Pharmaceuticals (formerly The Liposome Company) and the New Jersey Center for Biomaterials. D. Auguste acknowledges the 1930 Wallace Memorial fellowship from the Princeton University Graduate School. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2006/4

Y1 - 2006/4

N2 - Triggered release of adsorbed polymers from liposomes enables protection against immune recognition during circulation and subsequent intracellular delivery of DNA. Polycationic blocks, poly[2-(dimethylamino) ethyl methacrylate] (DMAEMA) (0.8, 3.1, 4.9, or 9.8 kg/mol) or polylysine (K) (3 kg/mol), act as anchors for poly(ethylene glycol) (PEG) (2 or 5 kg/mol) protective blocks. In addition, a copolymer with 15 strictly alternating blocks of PEG (2 kg/mol) and cationic amine sites was evaluated as a protective coating. Incorporation of 1,2-dioleoyl-3-dimethylammonium-propane, a titratable lipid with a pKa of ∼6.7, allows the liposome's net charge to increase as the pH shifts from 7.4 in the bloodstream to 5.5 in the endosome. The increased net liposome cationicity results in decreased cationic polymer adsorption. The EMPEG113-DMAEMA31 and EMPEG113-DMAEMA62 association constants decrease from 3.1 and 6.2 (mg/m2)/(mg/ml) at pH 7.4 to 1.7 and 3.2 (mg/m 2)/(mg/ml) at pH 5.5, respectively. However, EMPEG45-DMAEMA5, EMPEG45-DMAEMA20, and EMPEG45-N-DP15 did not show a strong response to changes in pH. Cationic polymer adsorption exceeds calculated values for liposome neutralization, resulting in adsorption profiles in the brush regime.

AB - Triggered release of adsorbed polymers from liposomes enables protection against immune recognition during circulation and subsequent intracellular delivery of DNA. Polycationic blocks, poly[2-(dimethylamino) ethyl methacrylate] (DMAEMA) (0.8, 3.1, 4.9, or 9.8 kg/mol) or polylysine (K) (3 kg/mol), act as anchors for poly(ethylene glycol) (PEG) (2 or 5 kg/mol) protective blocks. In addition, a copolymer with 15 strictly alternating blocks of PEG (2 kg/mol) and cationic amine sites was evaluated as a protective coating. Incorporation of 1,2-dioleoyl-3-dimethylammonium-propane, a titratable lipid with a pKa of ∼6.7, allows the liposome's net charge to increase as the pH shifts from 7.4 in the bloodstream to 5.5 in the endosome. The increased net liposome cationicity results in decreased cationic polymer adsorption. The EMPEG113-DMAEMA31 and EMPEG113-DMAEMA62 association constants decrease from 3.1 and 6.2 (mg/m2)/(mg/ml) at pH 7.4 to 1.7 and 3.2 (mg/m 2)/(mg/ml) at pH 5.5, respectively. However, EMPEG45-DMAEMA5, EMPEG45-DMAEMA20, and EMPEG45-N-DP15 did not show a strong response to changes in pH. Cationic polymer adsorption exceeds calculated values for liposome neutralization, resulting in adsorption profiles in the brush regime.

KW - Adsorption

KW - Controlled drug release

KW - Drug delivery

KW - Gene therapy

KW - Liposomes

KW - Polyethylene oxide

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AN - SCOPUS:30944465004

SN - 0142-9612

VL - 27

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EP - 2608

JO - Biomaterials

JF - Biomaterials

IS - 12

ER -

PH triggered release of protective poly(ethylene glycol)-b-polycation copolymers from liposomes

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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