New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery

Abstract

Design of an efficient site-specific drug delivery system based on degradable functional polymers still remains challenging. In this work, we synthesized and characterized three degradable functional polyesters belonging to the poly(malic acid) family: the poly(benzyl malate) (PMLABe), the poly(ethylene glycol)-b-poly(benzyl malate) (PEG42-b-PMLABe), the biotin-poly(ethylene glycol)-bpoly( benzyl malate) (Biot-PEG62-PMLABe). Starting from these building blocks, we were able to prepare the corresponding well-defined degradable functional nanoparticles whose toxicity was evaluated in vitro on normal and cancer cell lines. Results have evidenced that the prepared nanoparticles did not show any significant cytotoxicity even at high concentrations. A model anti-cancer drug (doxorubicin, Dox) or a fluorescent probe (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, DiD oil) has been encapsulated into PMLABe, PEG42-PMLABe or Biot-PEG62-PMLABe based nanoparticles in order to evaluate, respectively, the in vitro cytotoxicity of Dox-loaded nanoparticles on normal and cancer cell lines and the ligand (biotin) effect on cellular uptake in vitro using mmt 060562 cell line. Dox-loaded PMLABe, PEG42-PMLABe or Biot-PEG62-PMLABe nanoparticles showed an in vitro cytotoxicity similar to that of free Dox. Moreover, the DiD oil loaded Biot-PEG62-PMLABe based nanoparticles showed a better in vitro cellular uptake than ligand-free DiD oil loaded nanoparticles. Both results evidence the great potential of such degradable functional poly(malic acid) derivatives for the design of highly efficient site-specific anti-cancer nanovectors.

Taxonomy ofAureobasidiumspp. and biosynthesis and regulation of their extracellular polymers

“…Furthermore, water-insoluble PMA derivatives have been used to make various solid devices, compression molded pellets, films, microparticles, nano-conjugate and nanoparticles for specific drug delivery systems (Huang et al, 2012). Especially, it has versatile pendant carboxy group which allows the introduction of biologically active molecules and/or a targeting moiety via appropriate chemical modifications.…”

New promising biodegradable polyesters derived from poly((R,S)-3,3-dimethylmalic acid) for cardiovascular applications

“…Biopolyesters are widely recommended in biomedical applications [1] as drug carriers [2] such as poly(L-lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε--caprolactone) (PCL) [3], and poly(malic acid) (PMLA) [4][5][6][7][8]. These biodegradable polyesters were used either alone or as copolymers side chains to improve their mechanical properties, hydrolysis, long-term biodegradation, or biocompatibility behavior for the desired therapeutic applications (PLGA [9,10], PLMA [11][12][13][14][15], etc.).…”

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

“…However, since 2003, no work was published despites the great interest of the poly(malic acid) derivatives for the design of efficient biocompatible drug nanocarriers . These polyesters are mainly obtained by chemical ROP of the MLABe or its derivatives, or by chemical modification of naturally available PMLA . In this context, we have chosen to study the lipase‐catalyzed ROP of MLABe with the goal to obtain initiator‐free polymers for application in the drug delivery system field.…”