Transferrin-Conjugated Docetaxel–PLGA Nanoparticles for Tumor Targeting: Influence on MCF-7 Cell Cycle

Abstract

Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-l-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 32 full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G2/M phase.

Sucupira Oil-Loaded Nanostructured Lipid Carriers (NLC): Lipid Screening, Factorial Design, Release Profile, and Cytotoxicity

“…Sucupira oil-NLC (formulation no. 6) was placed onto Franz diffusion cell for the recording of the release profile values, which were fitted into four mathematical models (Figure 3) [67]. The release profiles of sucupira oil from NLC followed a sustained fashion over the course of 8 h. Within the first hour only about 17.5% of oil has been released from NLC, whereas at the end of the 8 h the cumulative amount reached 30% of the loaded oil.…”

Engineering precision nanoparticles for drug delivery

“…Therapeutics can be encapsulated within the NP core, entrapped in the polymer matrix, chemically conjugated to the polymer or bound to the NP surface. This enables delivery of various payloads including hydrophobic and hydrophilic compounds, as well as cargos with different molecular weights such as small molecules, biological macromolecules, proteins and vaccines [30][31][32][33][34][35] , making polymeric NPs ideal for co-delivery applications 36 . By modulating properties such as composition, stability, responsivity and surface charge, the loading efficacies and release kinetics of these therapeutics can be precisely controlled 37,38 .…”

Perillaldehyde 1,2-epoxide Loaded SLN-Tailored mAb: Production, Physicochemical Characterization and In Vitro Cytotoxicity Profile in MCF-7 Cell Lines

“…Cationic nanoparticles with a net positive surface charge have been proposed to further enhance cellular interaction and increase the cellular uptake of the loaded drug [1][2][3][4][5][6]. Site-specific delivery can be achieved via active targeting by surface modifying, such as with antibodies, aptamers and other targeting moieties (e.g., transferrin, folate) tailored to specific receptors [7,8].…”