Synthesis and Characterization of a Poly(ethylene Glycol)-Poly(simvastatin) Diblock Copolymer

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2014 Nov 29

PMID 25431653

Citations 6

Authors

Theodora A Asafo-Adjei

Thomas D Dziubla

David A Puleo

Affiliations

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Abstract

Biodegradable polyesters are commonly used as drug delivery vehicles, but their role is typically passive, and encapsulation approaches have limited drug payload. An alternative drug delivery method is to polymerize the active agent or its precursor into a degradable polymer. The prodrug simvastatin contains a lactone ring that lends itself to ring-opening polymerization (ROP). Consequently, simvastatin polymerization was initiated with 5 kDa monomethyl ether poly(ethylene glycol) (mPEG) and catalyzed via stannous octoate. Melt condensation reactions produced a 9.5 kDa copolymer with a polydispersity index of 1.1 at 150 °C up to a 75 kDa copolymer with an index of 6.9 at 250 °C. Kinetic analysis revealed first-order propagation rates. Infrared spectroscopy of the copolymer showed carboxylic and methyl ether stretches unique to simvastatin and mPEG, respectively. Slow degradation was demonstrated in neutral and alkaline conditions. Lastly, simvastatin, simvastatin-incorporated molecules, and mPEG were identified as the degradation products released. The present results show the potential of using ROP to polymerize lactone-containing drugs such as simvastatin.

Citing Articles

Synthesis, Hydrolytic Degradation Behavior, and Surface Properties of Poly(alkyl glycolide)-Polyglycolide Copolymers.

Canturk Bamyaci M, Cetin D, Cengiz C, Belen S, Mert O, Cengiz U ACS Omega. 2025; 10(8):8499-8511.

PMID: 40060789 PMC: 11886707. DOI: 10.1021/acsomega.4c10768.

Vancomycin- and Poly(simvastatin)-Loaded Scaffolds with Time-Dependent Development of Porosity.

Thilanga Liyanage A, Chen A, Puleo D, Joseph Halcomb 3rd F ACS Appl Bio Mater. 2021; 2(6):2511-2519.

PMID: 33912813 PMC: 8078142. DOI: 10.1021/acsabm.9b00207.

Biodegradable polymerized simvastatin stimulates bone formation.

Venkatesan N, Thilanga Liyanage A, Castro-Nunez J, Asafo-Adjei T, Cunningham L, Dziubla T Acta Biomater. 2019; 93:192-199.

PMID: 31055123 PMC: 6615997. DOI: 10.1016/j.actbio.2019.04.059.

Biodegradable Simvastatin-Containing Polymeric Prodrugs with Improved Drug Release.

Thilanga Liyanage A, Chen A, Puleo D ACS Biomater Sci Eng. 2019; 4(12):4193-4199.

PMID: 30631799 PMC: 6322697. DOI: 10.1021/acsbiomaterials.8b00884.

Tuning Properties of Poly(ethylene glycol)--poly(simvastatin) Copolymers Synthesized via Triazabicyclodecene.

Asafo-Adjei T, Dziubla T, Puleo D React Funct Polym. 2017; 119:37-46.

PMID: 29217967 PMC: 5714509. DOI: 10.1016/j.reactfunctpolym.2017.07.004.

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