Biocatalytic Route for the Synthesis of Oligoesters of Hydroxy-Fatty acids and ϵ-Caprolactone

Abstract

Developments of past years placed the bio-based polyesters as competitive substitutes for fossil-based polymers. Moreover, enzymatic polymerization using lipase catalysts has become an important green alternative to chemical polymerization for the synthesis of polyesters with biomedical applications, as several drawbacks related to the presence of traces of metal catalysts, toxicity and higher temperatures could be avoided. Copolymerization of ϵ-caprolactone (CL) with four hydroxy-fatty acids (HFA) from renewable sources, 10-hydroxystearic acid, 12-hydroxystearic acid, ricinoleic acid, and 16-hydroxyhexadecanoic acid, was carried out using commercially available immobilized lipases from Candida antarctica B, Thermomyces lanuginosus, and Pseudomonas stutzeri, as well as a native lipase. MALDI-TOF-MS and 2D-NMR analysis confirmed the formation of linear/branched and cyclic oligomers with average molecular weight around 1200 and polymerization degree up to 15. The appropriate selection of the biocatalyst and reaction temperature allowed the tailoring of the non-cyclic/cyclic copolymer ratio and increase of the total copolymer content in the reaction product above 80%. The catalytic efficiency of the best performing biocatalyst (Lipozyme TL) is evaluated during four reaction cycles, showing excellent operational stability. The thermal stability of the reaction products is assessed based on TG and DSC analysis. This new synthetic route for biobased oligomers with novel functionalities and properties could have promising biomedical applications.

Biocatalytic Approach for Novel Functional Oligoesters of ε-Caprolactone and Malic Acid

“…Lipases are particularly valuable for the ROP reactions of lactones [16], allowing the synthesis of polymers/oligomers and copolymers/co-oligomers in controlled reaction conditions and suited for biomedical applications, avoiding the toxicity effects of trace amounts of the metal catalyst, e.g., PCL-b-PEG-b-PCL triblock copolymers with polyethylene glycol [17]. The previous works of our group demonstrated the synthetic possibilities towards various co-oligomers of ECL with δ-gluconolactone [18][19][20], 5-hydroxymethyl-2-furancarboxylic acid [21], and fatty hydroxy acids [22][23][24]. The importance of copolymers derived from ECL is emphasized by novel reports on the possibilities to obtain this monomer from phenol by a chemoenzymatic process [25].…”

“…The immobilized biocatalyst (15 mg) was added to the reaction mixture, and the reactions were performed under continuous stirring at 1200 rpm for 24 h at 70 • C using an Eppendorf Thermomixer Comfort heating shaker (Eppendorf, Hamburg, Germany). These experimental methodology and reaction parameters were set based on the previous results concerning polymerization reactions of hydroxy acids with ECL [21,23]. At the end of the reaction, the enzyme was separated from the reaction mixture by filtration, followed by removal of the solvent by vacuum-drying at room temperature.…”

Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

“…The aim of this work was to prepare anticancer drug-loaded polymeric nanoparticles from a biodegradable and biocompatible oligomer, co-encapsulating sorafenib and cisplatin, which can become effective sustained and targeted drug delivery devices. The oligomer was obtained through a green biocatalytic route, from ε-caprolactone and 12-hydroxystearic acid using a microbial lipase, as previously reported [ 24 ], and was proved to be efficient for the nanoencapsulation of sorafenib [ 25 ]. It belongs to a new class of biobased oligomers of hydroxy acids, which are increasingly considered for biomedical and cosmetic applications [ 26 ].…”

(R)-10-Hydroxystearic Acid: Crystals vs. Organogel

“…As the chemical synthesis of the compound is not straight forward, we took advantage of the recently published preparation route for (R)-10-HSA that employs a probiotic bacterium, commonly available at as an over-the-counter pharmaceutical preparation able to yield a product with excellent enantiomeric excess through hydration of oleic acid [21]. The industrial interest for (R)-10-HSA stems from the possible application of this precursor for the preparation of bio-based polymers [22] and for the synthesis of flavors [23] beside the better-known uses in cosmetics [24]. In this field, (R)-10-HSA looks extremely interesting owing to its two-fold action, namely as an active ingredient and texture modifier, thanks to its potential thickening and organogelling abilities.…”