A biomedical library of serinol-derived polyesters

Rickerby, Jenny; Prabhakar, Roopa; Patel, Anita; Knowles, Jonathan C.; Brocchini, Steve

doi:10.1016/j.jconrel.2004.07.021

Cited by 12 publications

(7 citation statements)

References 27 publications

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“…[ 2 ] Accordingly, it is now possible to construct new materials with a large range of physicochemical properties and, of significant importance, from building blocks which are either already in clinical use, [ 3 ] or which have relatively low barriers to translation. [ 4 ] However, for diseases including many cancers, there remain multiple unknowns concerning how such new materials might overcome the key barriers to drug delivery, namely, the ability to concentrate a therapeutic agent in a target site in sufficient dose and for sufficient time to afford an efficacious response. The potential advantages of polymer pro‐drugs are that they can be designed to release drugs either at a controlled rate in plasma to ensure drug concentrations remain in the therapeutic window, or they can be encoded with functionality to ensure that release only occurs in the disease site.…”

Section: Introductionmentioning

confidence: 99%

Functionalized Block Co‐Polymer Pro‐Drug Nanoparticles with Anti‐Cancer Efficacy in 3D Spheroids and in an Orthotopic Triple Negative Breast Cancer Model

Taresco

Abelha

Cavanagh

et al. 2020

Advanced Therapeutics

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Amphiphilic block co-polymers composed of poly(ethylene glycol)-co-poly(lactide)-co-poly(2-((tert-butoxycarbonyl)amino)-3-propyl carbonate) (PEG-pLA-pTBPC) are synthesized in monomer ratios and arrangements to enable assembly into nanoparticles with different sizes and architectures. These materials are based on components in clinical use, or known to be biodegradable, and retain the same fundamental chemistry across "AB" and "BAB" block architectures. In MCF7 and MDA-MB-231 breast cancer cells, nanoparticles of <100 nm are internalized most rapidly, by both clathrin-and caveolin-mediated pathways. In THP-1 cells, polymer architecture and length of the hydrophilic block is the most important factor in the rate of internalization. The organ distributions of systemically injected nanoparticles in healthy mice indicate highest accumulation of the BAB-blocks in lungs and liver and the lowest accumulation in these organs of a methoxyPEG 5000-pLA-pTBPC polymer. Conjugation of doxorubicin via a serum-stable urea linker to the carbonate regions of PEG 5000-pLA-pTBPC generates self-assembling nanoparticles which are more cytotoxic in 2D, and penetrate further in 3D spheroids of triple negative breast cancer cells, than the free drug. In an aggressive orthotopic triple negative breast cancer mouse model, the methoxyPEG 5000-pLA-pTBPC is of similar potency to free doxorubicin but with no evidence of adverse effects in terms of body weight.

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Section: Introductionmentioning

confidence: 99%

Functionalized Block Co‐Polymer Pro‐Drug Nanoparticles with Anti‐Cancer Efficacy in 3D Spheroids and in an Orthotopic Triple Negative Breast Cancer Model

Taresco

Abelha

Cavanagh

et al. 2020

Advanced Therapeutics

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“…The –OH groups can react with the diisocyanate and the –NH 2 group can be protected for further biofunctioanlization. Equally important is the biocompatibility of serinol [28, 29]. We chose hexamethylene diisocyanate (HDI) because it has been used in many polyurethanes [30–33].…”

Section: Introductionmentioning

confidence: 99%

A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer

Park

Wang

2011

Biomaterials

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Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and 1 H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32°C and reached maximum elastic modulus at 37°C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine.

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“…Serinol was selected for the polymer synthesis because of its proven biocompatibility as a monomer for biodegradable polyesters. 13 A coupling reaction between TMBQ-succinimidyl ester and serinol consequently yielded a diol with a pendant TMBQ (compound 1). Synthesized serinol monomer was successfully confirmed by 1 H and 13 C NMR spectroscopy and elemental analysis.…”

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confidence: 99%

“…13 A coupling reaction between TMBQ-succinimidyl ester and serinol consequently yielded a diol with a pendant TMBQ (compound 1). Synthesized serinol monomer was successfully confirmed by 1 H and 13 C NMR spectroscopy and elemental analysis. The serinol monomer was polymerized by the reaction described in Scheme 2.…”

mentioning

confidence: 99%