Construction and application of biotin–poloxamer conjugate micelles for chemotherapeutics

Abstract

Biotin was conjugated on poloxamer to prepare biotin-poloxamer (BP) conjugate micelles for chemotherapeutics. Epirubicin (EPI) was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized in terms of size, ζ-potential, morphology, drug loading, drug encapsulation and drug release. Marrow leukemic HL-60 cells were used for evaluating the in vitro cytotoxicity of EPI-loaded BP micelles. Nude mice were axillainoculated subcutaneously HL-60 cells to establish tumour model for investigating the inhibition effects of EPI-loaded BP micelles. From the results, the sizes of these nanoparticles were about 100 nm. Fluorescence microscope observation supported the enhanced cellular uptake of the micelles. The order of the inhibition on tumour volume growth was: EPI-loaded BP micelles >EPI-loaded MATP micelles >EPI-loaded poloxamer micelles >EPI. BP micelles showed significant antitumour activity and low toxicity, compared with the non-targeted micelles. With the advantage of EPR effect and tumour-targeting potential, BP conjugate micelles might be developed as a new system for chemotherapeutics.

Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery

“…Likewise, DOX-linker 1-Fbg microspheres were fabricated with approximately 10 µm diameter and highly porous surface ( Figure 3D-F). Degradation of bare-Fbg microspheres was analyzed ( Figure 4A and B), degradation of DOX-(3-MAH)-Fbg microspheres was analyzed ( Figure 4C and D), and Degradation of DOX-SM(PEG) 12 -Fbg was analyzed ( Figure 4E and F).…”

“…Consequently, 22.44%±2.13% of DOX was loaded onto Fbg, and approximately three DOX molecules seemed to be attached to each Fbg molecule. For the non-cleavable drug conjugation, the N-hydroxysuccinimide ester part of SM(PEG) 4 and SM(PEG) 12 was conjugated to a 3′-C amino group of DOX, forming a relatively stable amide bond, and a maleimide group of SM(PEG) 4 and SM(PEG) 12 was cross-linked to Fbg by a thioester bond. DOX (33.10%±2.41%) was loaded onto Fbg with SM(PEG) 4 , having a DOX/Fbg ratio of 4.11, and 45.25%±2.45% of DOX was carried to Fbg with SM(PEG) 12 , showing 5.95 molecules on a Fbg molecule.…”

“…The DOX-(3-MAH)-Fbg (30 mg), DOX-SM(PEG) 4 Fbg (20 mg), or DOX-SM(PEG) 12 -Fbg (15 mg) microspheres, equivalent to 100 µg of DOX, which was calculated from drug loading efficiencies, was put in the device. Free DOX (100 µg) and bare-Fbg microspheres were incorporated into two more devices containing PBS (pH 7.3), which were used as a positive control and a negative control, respectively.…”

“…To investigate the length effect of linkers, DOX was covalently attached to Fbg by non-cleavable linkers: SM(PEG) 4 (L3, n=4) and SM(PEG) 12 (L5, n=12), as outlined in Figure 1B. DOX (1.5 mg, 2.76 µmol) was mixed with SM(PEG) 4 (1.6 mg, 3.12 µmol) or SM(PEG) 12 (2.6 mg, 3.00 µmol) in 1 mL of PBS (pH 7.2) and stirred using an orbital shaker (250 rpm) at 25°C for 24 hours, forming stable DOX-linker (DOX-L3, DOX-L5) complexes through an amide bond.…”

“…For example, an arginine-glycine-aspartate (RGD) peptide as a tumor-targeting moiety was conjugated onto the albumin nanoparticles with gemcitabine, inhibiting pancreatic tumor cell growth. 10 Furthermore, various targeting molecules, such as folic acid 11 and biotin, 12 have been extensively investigated, demonstrating improved tumor specificity and reduced toxicity to normal cells.…”