Biodegradable Copolymer for Stimuli-Responsive Sustained Release of Doxorubicin

Abstract

Pendent functionalization of biodegradable polymers provides unique importance in biological applications. In this work, we have synthesized a polymeric nanocarrier for the controlled release of the anticancer drug doxorubicin (DOXI). Inspired by the pH responsiveness of acylhydrazine bonds along with the interesting self-assembly behavior of amphiphilic copolymers, this report delineates the development of a PEG-SS-PCL-DOXI copolymer consisting of DOXI, PEG, and a caprolactone backbone. First, the inclusion of a PEG moiety in the copolymer helps to achieve biocompatibility and aqueous solubility as well as a prolonged circulation time of the nanocarrier. Second, an acid-sensitive acylhydrazine-based linkage is chosen to attach DOXI to trigger sustained drug release, whereas the inclusion of an enzymatically cleavable disulfide linkage in the backbone adds to the advantage of backbone biodegradability at the intracellular level.

Polymer based Nano-Assemblies: Very Efficient Carrier in the Field of Cancer Chemotherapy

“…doxorubicin, camptothecin, cis-platin) suffer either from solubility or sitespecificity causes for severe side-effects in real applications [3]. To deal with these different drawbacks of small molecule drugs, researchers have employed different delivery vehicle carrying the chemotherapeutic agent either with non-covalent encapsulation or attached with different stimuli responsive (pH, thermal, and enzymatic) linkers to the delivery vehicle [3][4][5][6][7][8][9][10][11][12][13]. This vehicle carries single or multi drug component in aqueous environment form self-assembled nano-structure by protecting the drugs into its hydrophobic core and deliver the drug once it reaches to the affected area [3][4][5][6][7][8][9][10][11][12][13].…”

“…These all particularly form excellent nano-assemblies in aqueous environment due its amphiphilicity present in it [14][15][16][17][18]. Polymer based drug delivery system is one of those which form excellent nano-assemblies when it functionalized with hydrophilic PEG group [7,9,[11][12][13]. The drug can deliver through this nano-carrier either by non-covalent encapsulation or covalently attached with different stimuli responsive linkers [5,7,[13][14][15].…”

“…The drug can deliver through this nano-carrier either by non-covalent encapsulation or covalently attached with different stimuli responsive linkers [5,7,[13][14][15]. The polymer based nano-vehicle shows enhanced cytotoxic effect due to its plasma stability which eventually helps to increase the permeation and retention effect (EPR) [5][6][7][8][9][10][11][12][13][14][15]. Due to leaky vesicular nature of the blood vessel around the tumour help these nano-vehicles to reach the targeted sites [8].…”

“…Different polymeric methods with different backbones (e.g. ROP, poly-condensation, ROMP), have already been explored by different research groups to employ various functionalities for synthesizing smart carriers in the field of nano-medicine [5][6][7][8][9][10][11][12][13][14]. These different polymeric system shows excellent nanoassembly [5][6][7][8][9][10][11][12][13][14].…”

“…ROP, poly-condensation, ROMP), have already been explored by different research groups to employ various functionalities for synthesizing smart carriers in the field of nano-medicine [5][6][7][8][9][10][11][12][13][14]. These different polymeric system shows excellent nanoassembly [5][6][7][8][9][10][11][12][13][14]. Upon incorporation of drugs into that by either covalent or non-covalently form different shapes at nano-scale level and internalize inside the cell quite efficiently [5][6][7][8][9][10][11][12][13][14][15].…”