Biocatalytic Approach for the Synthesis of Glycerol‐Based Macroamphiphiles and their Self‐Assembly to Micellar Nanotransporters

Abstract

Glycerol is one of the most versatile and valuable chemical substances and is utilized in a variety of commercial products with no known adverse pharmacological or environmental effects. Moreover, it exhibits good chemical stability and inertness under biological conditions. We have designed and developed Candida antarctica lipase (CAL B) catalyzed biocatalytic method to synthesize novel polymeric systems using glycerol and poly[ethylene glycol bis(carboxymethyl) ether] dimethylester. Both synthons are biocompatible, non‐toxic, and are readily available. The polymerization occurs regioselectively through the primary hydroxyl groups of glycerol leaving the secondary hydroxyls for post‐polymerization chemical modifications and also for attaching drugs/bioactive molecules. We have utilized these sites for the synthesis of amphiphilic polymers by attaching alkyl chains at the secondary hydroxyl groups simply by acylation. The drug encapsulation abilities of the resulting polymers have been evaluated for potential biomedical applications.magnified image

Encapsulation and cellular internalization of cyanine dye using amphiphilic dendronized polymers

“…These were then grafted with alkyl chains (C 12 /C 14 /C 18 ) and / or the G1.0/G2.0 dendrons and hyperbranched polyglycerol moiety [25,26,27]. Herein, we have synthesized a newer class of biocompatible dendronized polymeric materials by using azidotriglycerol and following a chemo-enzymatic approach.…”

“…Since in biocatalytic condensation polymerization of azidoglycerol / azidotriglycerol, no chemical shift in the methine proton was observed in the 1 H NMR this undoubtedly confirm that the polymerization occurs through the primary hydroxyl groups leaving aside secondary hydroxyls intact.The polymeric systems described herein differs from the previously synthesized materials in the sense that by the incorporation of azidotriglycerol (2) for the copolymer synthesis provide two sites i.e. a hydroxyl group and azide moiety to further decorate the copolymer backbone for various applications[25,26,27,31]. The 'Click chemistry' approach was utilized for grafting hydrophobic (C 12 ) terminal alkynes and hydrophilic core propargylated polyglycerol dendron[G1.0] & [G2.0] moieties.However, additional C 12 aliphatic alkyl chains were also incorporated by using corresponding alkanoic acid through the esterification of secondary hydroxyl groups present on the backbone.…”

Synthesis of amphiphilic dendronized polymers to study their self‐assembly and transport behavior

“…PEG‐1000‐diol was first oxidized to the corresponding diacid ( 1 ) using alkaline KMnO 4 in aqueous media in an almost quantitative yield without further purification. The PEG‐1000 diacid ( 1 ) was then converted to diethyl ester derivative ( 2 ) by using standard esterification protocol (Scheme ).…”

“…We have adopted a “green” biocatalytic method to synthesize dendronized multiamphiphilic polymers by using biocompatible materials, e.g., poly(ethylene glycol), glycerol, polyglycerol (PG) dendrons, etc. Furthermore, the immobilized enzyme “Novozym 435” used is inexpensive, versatile, and commercially available, and its catalyzing characteristics have been studied in depth by us and others in polymer synthesis . Gross and Kobayashi have reported that Novozym 435 works more efficiently with hydrophobic substrates .…”

Sìntese de materiais poliméricos contendo moléculas bioativas e materiais de fontes renováveis via catálise enzimática

“…Glicerol é uma das mais versáteis e valiosas substancias químicas utilizadas em uma variedade de produtos comerciais, não sendo conhecidos efeitos adversos na área farmacológica e ambiental 33 . Apresenta uma boa estabilidade química sendo inerte em ambientes biológicos, sendo assim muito utilizado em biomoléculas 34 .…”