Abstract
The enzymatically synthesized poly (glycerol adipate) (PGA) has demonstrated all the desirable key properties required from a performing biomaterial to be considered a versatile “polymeric-tool” in the broad field of drug delivery. The step-growth polymerization pathway catalyzed by lipase generates a highly functionalizable platform while avoiding tedious steps of protection and deprotection. Synthesis requires only minor purification steps and uses cheap and readily available reagents. The final polymeric material is biodegradable, biocompatible and intrinsically amphiphilic, with a good propensity to self-assemble into nanoparticles (NPs). The free hydroxyl group lends itself to a variety of chemical derivatizations via simple reaction pathways which alter its physico-chemical properties with a possibility to generate an endless number of possible active macromolecules. The present work aims to summarize the available literature about PGA synthesis, architecture alterations, chemical modifications and its application in drug and gene delivery as a versatile carrier. Following on from this, the evolution of the concept of enzymatically-degradable PGA-drug conjugation has been explored, reporting recent examples in the literature.
Highlights
Interest in the use of enzymes in polymer synthesis as a greener alternative to traditional chemical polymerization has been growing for a number of years [1]
There are many advantages associated with enzymatic synthesis, including but not restricted to: (a) mild reaction conditions, (b) catalysts with low toxicity, high and tunable activity which are often recyclable, (c) the avoidance of toxic heavy metal catalysts, (d) often good linearity of products due to steric hindrance at the enzyme active site, (e) few by-products, and (f) less need for protection and deprotection steps [2,3,4,5]
In the present manuscript we have extensively retraced the evolution of the enzymatic synthesis
Summary
Interest in the use of enzymes in polymer synthesis as a greener alternative to traditional chemical polymerization has been growing for a number of years [1]. (e) few by-products, and (f) less need for protection and deprotection steps [2,3,4,5]. The chemo- and regioselectivity of lipase allows the hydroxyl moiety of the PGA backbone to remain intact, without the need for tedious and complicated protection and deprotection steps [9]. This hydroxyl moiety results in a polymer open to a variety of further functionalizations via simple and accessible chemistry. This work has led to a series of literature precedents/guidelines for future researchers interested in exploiting the advantages of PGA, and these will be summarized briefly here
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