Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin

Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl l-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24 h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The micelles based on mPEG-SS-PPLG were fabricated. SN-38 was loaded into micelles with high encapsulation efficiency. ► The active lactone ring of SN-38 was effectively protected by the micelles. ► The micelles showed reduction-sensitive drug release profiles. ► SN-38-loaded micelles showed essentially decreased cytotoxicity.