Optimization of lipase‐catalyzed polymerization of benzyl malolactonate through a design of experiment approach

Casajus, Hubert; Tranchimand, Sylvain; Wolbert, Dominique; Nugier‐Chauvin, Caroline; Cammas‐Marion, Sandrine

doi:10.1002/app.44604

Cited by 4 publications

(9 citation statements)

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“…Thus, the effect of various parameters (enzyme/MLABe ratio, aqueous phase/organic phase ratio, and stirring rate) was studied. However, given the large number of parameters that can influence the reaction, we have chosen to use a design of experiment approach to find the best conditions leading to well-defined high molar mass enzymatic PMLABe [43]. Using such an approach, we were able to find reaction conditions under which the expected enzymatic PMLABe were reproducibly synthesized [43].…”

Section: Resultsmentioning

confidence: 99%

“…The RS-PMLABe P5, the S-PMLABe P6, and the R-PMLABe P7 were obtained as described previously [43] by ring-opening polymerization of the RS-MLABe, R-MLABe, and S-MLABe, respectively, in the presence of porcine pancreatic lipase (PPL) with toluene. Experiments were realized in a 24-multi reactor Büchi Syncore Line.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, enzymatic polymerizations are, to date, less controlled than chemical ones [40,41,42]. Nevertheless, we recently set up conditions to synthesize well-defined poly(benzyl malate) (PMLABe) derivatives of high molar masses through the enzymatic polymerization of benzyl malolactonate (MLABe) in the presence of pancreatic porcine lipase (PPL) [43].…”

Section: Introductionmentioning

confidence: 99%

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Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages

et al. 2018

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The design of drug-loaded nanoparticles (NPs) appears to be a suitable strategy for the prolonged plasma concentration of therapeutic payloads, higher bioavailability, and the reduction of side effects compared with classical chemotherapies. In most cases, NPs are prepared from (co)polymers obtained through chemical polymerization. However, procedures have been developed to synthesize some polymers via enzymatic polymerization in the absence of chemical initiators. The aim of this work was to compare the acute in vitro cytotoxicities and cell uptake of NPs prepared from poly(benzyl malate) (PMLABe) synthesized by chemical and enzymatic polymerization. Herein, we report the synthesis and characterization of eight PMLABe-based polymers. Corresponding NPs were produced, their cytotoxicity was studied in hepatoma HepaRG cells, and their uptake by primary macrophages and HepaRG cells was measured. In vitro cell viability evidenced a mild toxicity of the NPs only at high concentrations/densities of NPs in culture media. These data did not evidence a higher biocompatibility of the NPs prepared from enzymatic polymerization, and further demonstrated that chemical polymerization and the nanoprecipitation procedure led to biocompatible PMLABe-based NPs. In contrast, NPs produced from enzymatically synthesized polymers were more efficiently internalized than NPs produced from chemically synthesized polymers. The efficient uptake, combined with low cytotoxicity, indicate that PMLABe-based NPs are suitable nanovectors for drug delivery, deserving further evaluation in vivo to target either hepatocytes or resident liver macrophages.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages

et al. 2018

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“…The different PMLABe were synthesized as described previously [10] by ring-opening polymerization of the MLABe in presence of the enzyme (PPL, CpLip2 or CpLip2_S180A) in Tris-HCl buffer pH7. Experiments were realized in a 24-multi reactor Büchi Syncore Line.…”

Section: Enzymatic Polymerization Of Mlabementioning

confidence: 99%

“…the β-substituted β-lactones also called alkyl malolactonates, to synthesize poly(malic acid) and its derivatives 10,11 . In a first step, we have established, through a Design of Experiment (DoE) procedure, the optimal experimental conditions to reproducibly synthesize poly(benzyl malate) with weight average molar masses varying from 5,000 to 13,000 g/mol, dispersities between 1.2 and 1.6 (depending on the conditions used for the polymerization) and hydrolysis rates lower than 5%, using PPL as catalyst 10 . PMLABe obtained through lipasecatalyzed ROP of MLABe were then formulated and the resulting nanoparticles were involved in several in vitro assays whose results have highlighted the influence of the polymer synthesis method on cell viability in particular 11 .…”

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confidence: 99%

Lipase-Catalyzed Ring-Opening Polymerization of Benzyl Malolactonate: An Unusual Mechanism?

et al. 2020

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Evaluation of biocatalytic pathways in the synthesis of polyesters: Towards a greener production of surgical sutures

Nicolás

Lassalle

Ferreira

2022

Polymers for Advanced Techs

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This review presents an updated and alternative perspective on enzymatic synthesis to obtain polyesters, with a focus on the precursor materials for absorbable sutures: poly‐lactic, poly‐glycolic, and poly‐lactic‐co‐glycolic acids. Currently, the profitable path towards the industrial synthesis of polyesters is ring‐opening polymerization (ROP) of lactones, which is an experimentally complex process and implies a hazardous environmental impact due to the need for energy consumption, use of large volumes of toxic organic solvents and of non‐biocompatible metal‐based catalysts. On the contrary, enzymatically driven reactions may be performed under mild conditions in simple reactors. Mechanistic and experimental issues of the two major biocatalyzed strategies ‐direct condensation and ROP‐ were analyzed from a green chemistry perspective. These enzyme‐catalyzed poly‐esterifications often return low yield and/or low final molecular weight (Mw). Considering all the analyzed published data available, possible strategies to overcome these limitations were postulated: implementation of aqueous biphasic reaction systems, use of ultrasound agitation and sequential addition of reactants or co‐solvents. To promote Mw increment, post‐reaction treatments can be carried out such as thermally induced short‐chain polymerization under vacuum and incorporation of glycols as chain extenders.

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Optimization of lipase‐catalyzed polymerization of benzyl malolactonate through a design of experiment approach

Cited by 4 publications

References 37 publications

Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages

Cell Uptake and Biocompatibility of Nanoparticles Prepared from Poly(benzyl malate) (Co)polymers Obtained through Chemical and Enzymatic Polymerization in Human HepaRG Cells and Primary Macrophages

Lipase-Catalyzed Ring-Opening Polymerization of Benzyl Malolactonate: An Unusual Mechanism?

Evaluation of biocatalytic pathways in the synthesis of polyesters: Towards a greener production of surgical sutures

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