Biodegradable Stereocomplex Micelles Based on Dextran-block-polylactide as Efficient Drug Deliveries

Abstract

Biodegradable stereocomplex micelles (SCMs) based on amphiphilic dextran-block-polylactide (Dex-b-PLA) were designed and used for efficient intracellular drug deliveries. The Dex-b-PLA copolymers were successfully synthesized by click reaction. The structures of the resultant copolymers were verified by (1)H NMR and FT-IR spectra. The formation of stable micelles through self-assembly driven by the stereocomplexation between enantiomeric l- and d-PLA blocks was characterized by transmission electron microscopy (TEM), dynamic laser scattering (DLS), and fluorescence techniques. It was interesting to observe that the SCMs showed lower critical micelle concentration values (CMCs) because of the stereocomplex interaction between PLLA and PDLA. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis provided information on the thermal and crystal properties of the copolymers and SCMs. The improved stability of SCMs should be attractive for intracellular drug delivery. Thus, a model anticancer drug doxorubicin (DOX) was loaded into micelles, and the in vitro drug release in was also studied. The release kinetics of DOX showed DOX-loaded SCMs exhibited slower DOX release. Confocal laser scanning microscopy (CLSM) and flow cytometry studies also showed that the DOX-loaded SCMs exhibited a slower drug release behavior. Meanwhile, the MTT assay demonstrated that DOX-loaded SCMs show lower cellular proliferation inhibition against HepG2. In sum, the micelles through self-assembly driven by stereocomplex interaction would have great potential to be used as stable delivery vehicles for pharmaceutical and biomedical applications.

Humid Heat Autoclaving of Hybrid Nanoparticles Achieved by Decreased Nanoparticle Concentration and Improved Nanoparticle Stability Using Medium Chain Triglycerides as a Modifier

“…And according to the results of the researches subjecting either PCL homopolymer or PCL containing block copolymers to hydrolysis (5,(8)(9)(10), enzymolysis (11)(12)(13) or even heating (14), the chemical structure of the block copolymers could be reinforced by changing their block composition (5,10,15) or modifying the copolymers with different pendent groups (9). At particle level, the stability of nanoparticles could be improved by electrostatic coating (16)(17)(18), core/shell crosslinking (19)(20)(21) or stereocomplex formation (22,23).…”

Nanoparticles of alkylglyceryl-dextran-graft-poly(lactic acid) for drug delivery to the brain: Preparation and in vitro investigation

“…http Poly(lactic acid) (PLA) is commonly used for various tissue engineering and drug delivery applications not only due to its biodegradability, biocompatibility and to being non-immunoactive, but also due to its capacity to form colloidal systems of low polydispersity [12,13]. While the hydrophobicity of pure PLA nanoparticles normally leads to a rapid removal from the bloodstream by the reticulo-endothelial system upon iv injection [14], this shortcoming may be addressed by modification with hydrophilic materials of natural origin, such as dextran [15][16][17]. Considered non-toxic and non-immunogenic, dextran has been used historically as a safe plasma expander [18] and also to impart stabilisation in the blood-stream and ''stealth'' properties to injectable nanoparticles [19,20].…”

Micro- and nanostructures of polylactide stereocomplexes and their biomedical applications

“…40 Dextran-block-PLA copolymers were used for the preparation of stereocomplex micelles and encapsulation of doxorubicin. 41 Stereocomplex micelles have shown slower intracellular doxorubicin release and lower growth inhibition efficiency of HepG2 cells in comparison to micelles formed from linear polymers.…”