Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin
Poly(acrylic acid) (PAA) was grafted onto both termini of Pluronic F87 (PEO₆₇-PPO₃₉-PEO₆₇) via atom transfer radical polymerization to produce a novel muco-adhesive block copolymer PAA₈₀-b-F₈₇-b-PAA₈₀. It was observed that PAA₈₀-F₈₇-PAA₈₀ forms stable complexes with weakly basic anti-cancer drug, Do...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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2004
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| Online Access: | http://hdl.handle.net/1721.1/7498 |
| _version_ | 1826215374968848384 |
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| author | Tian, Y. Ravi, P. Bromberg, Lev Hatton, T. Alan Tam, K. C. |
| author_facet | Tian, Y. Ravi, P. Bromberg, Lev Hatton, T. Alan Tam, K. C. |
| author_sort | Tian, Y. |
| collection | MIT |
| description | Poly(acrylic acid) (PAA) was grafted onto both termini of Pluronic F87 (PEO₆₇-PPO₃₉-PEO₆₇) via atom transfer radical polymerization to produce a novel muco-adhesive block copolymer PAA₈₀-b-F₈₇-b-PAA₈₀. It was observed that PAA₈₀-F₈₇-PAA₈₀ forms stable complexes with weakly basic anti-cancer drug, Doxorubicin. Thermodynamic changes due to the drug binding to the copolymer were assessed at different pH by isothermal titration calorimetry (ITC). The formation of the polymer/drug complexes was studied by turbidimetric titration and dynamic light scattering. Doxorubicin and PAA-b-F87-b-PAA block copolymer are found to interact strongly in aqueous solution via non-covalent interactions over a wide pH range. At pH>4.35, drug binding is due to electrostatic interactions. Hydrogen-bond also plays a role in the stabilization of the PAA₈₀-F₈₇-PAA₈₀/DOX complex. At pH 7.4 (α=0.8), the size and stability of polymer/drug complex depend strongly on the doxorubicin concentration. When CDOX <0.13mM, the PAA₈₀-F₈₇-PAA₈₀ copolymer forms stable inter-chain complexes with DOX (110 ~ 150 nm). When CDOX >0.13mM, as suggested by the light scattering result, the reorganization of the polymer/drug complex is believed to occur. With further addition of DOX (CDOX >0.34mM), sharp increase in the turbidity indicates the formation of large aggregates, followed by phase separation. The onset of a sharp enthalpy increase corresponds to the formation of a stoichiometric complex. |
| first_indexed | 2024-09-23T16:26:18Z |
| format | Article |
| id | mit-1721.1/7498 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:26:18Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | mit-1721.1/74982019-04-10T21:49:02Z Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin Tian, Y. Ravi, P. Bromberg, Lev Hatton, T. Alan Tam, K. C. Poly(acrylic acid) Pluronic F87 atom transfer radical polymerization ATRP muco-adhesive block copolymers CDOX Doxorubicin Poly(acrylic acid) (PAA) was grafted onto both termini of Pluronic F87 (PEO₆₇-PPO₃₉-PEO₆₇) via atom transfer radical polymerization to produce a novel muco-adhesive block copolymer PAA₈₀-b-F₈₇-b-PAA₈₀. It was observed that PAA₈₀-F₈₇-PAA₈₀ forms stable complexes with weakly basic anti-cancer drug, Doxorubicin. Thermodynamic changes due to the drug binding to the copolymer were assessed at different pH by isothermal titration calorimetry (ITC). The formation of the polymer/drug complexes was studied by turbidimetric titration and dynamic light scattering. Doxorubicin and PAA-b-F87-b-PAA block copolymer are found to interact strongly in aqueous solution via non-covalent interactions over a wide pH range. At pH>4.35, drug binding is due to electrostatic interactions. Hydrogen-bond also plays a role in the stabilization of the PAA₈₀-F₈₇-PAA₈₀/DOX complex. At pH 7.4 (α=0.8), the size and stability of polymer/drug complex depend strongly on the doxorubicin concentration. When CDOX <0.13mM, the PAA₈₀-F₈₇-PAA₈₀ copolymer forms stable inter-chain complexes with DOX (110 ~ 150 nm). When CDOX >0.13mM, as suggested by the light scattering result, the reorganization of the polymer/drug complex is believed to occur. With further addition of DOX (CDOX >0.34mM), sharp increase in the turbidity indicates the formation of large aggregates, followed by phase separation. The onset of a sharp enthalpy increase corresponds to the formation of a stoichiometric complex. Singapore-MIT Alliance (SMA) 2004-12-16T06:15:15Z 2004-12-16T06:15:15Z 2005-01 Article http://hdl.handle.net/1721.1/7498 en Molecular Engineering of Biological and Chemical Systems (MEBCS); 26912 bytes application/pdf application/pdf |
| spellingShingle | Poly(acrylic acid) Pluronic F87 atom transfer radical polymerization ATRP muco-adhesive block copolymers CDOX Doxorubicin Tian, Y. Ravi, P. Bromberg, Lev Hatton, T. Alan Tam, K. C. Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title | Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title_full | Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title_fullStr | Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title_full_unstemmed | Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title_short | Synthesis and Aggregation Behavior of Pluronic F87/Poly(acrylic acid) Block Copolymer with Doxorubicin |
| title_sort | synthesis and aggregation behavior of pluronic f87 poly acrylic acid block copolymer with doxorubicin |
| topic | Poly(acrylic acid) Pluronic F87 atom transfer radical polymerization ATRP muco-adhesive block copolymers CDOX Doxorubicin |
| url | http://hdl.handle.net/1721.1/7498 |
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