Abstract
The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM) self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol) (PEG), and dextrorotatory and levorotatory polylactides (PDLA and PLLA) was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC) than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT) as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE) and the slowest drug release in phosphate-buffered saline (PBS) at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic.
Highlights
Polylactide (PLA) derived from lactic acid is known as one kind of biodegradable and biocompatible aliphatic polyester and is classified as a grade generally recognized as safe (GRAS) by US Food and Drug Administration (FDA) [1]
As depicted in Scheme 1, the amphiphilic enantiomeric PLA–poly(ethylene glycol) (PEG)–PLA copolymers were synthesized through the ring-opening polymerization (ROP) of LA with PEG as a macroinitiator and Sn(Oct)2 as a catalyst
The obtained amphiphilic copolymers and their equimolar mixture self-assembled into micelles in aqueous solution driven by microphase separation
Summary
Polylactide (PLA) derived from lactic acid is known as one kind of biodegradable and biocompatible aliphatic polyester and is classified as a grade generally recognized as safe (GRAS) by US Food and Drug Administration (FDA) [1]. The easy clearance and good security make PLA a great potential candidate for biomedical applications, including medical devices [2], tissue engineering [3,4], drug delivery [5,6], and so on. For successful use of PLA in drug delivery, hydrophobicity is one of the serious challenges. The hydrophobicity of PLA is difficult to be dispersed in water and easy to be uptaken by a mononuclear phagocyte system (MPS), resulting in the limitation in circulation [7]. One of the most effective approaches to address this problem is to introduce hydrophilic blocks, such as polyzwitterions and poly(ethylene glycol) (PEG) into PLA, synthesizing amphiphilic PLA-containing copolymers [7]. The hydrophilic coronas ensure the water-solubility, anti-protein adsorption, and long circulation time, and the hydrophobic PLA regions serve as a reservoir of hydrophobic drugs.
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