Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/62392

TitleTransferrin-conjugated docetaxel-PLGA nanoparticles for tumor targeting: influence on MCF-7 cell cycle
Author(s)Jose, Sajan
Cinu, Thomas A.
Sebastian, Rosmy
Shoja, M. H.
Aleykutty, N. A.
Durazzo, Alessandra
Lucarini, Massimo
Santini, Antonello
Souto, Eliana
Keywordstransferrin conjugate
tumor targeting
docetaxel trihydrate
PLGA nanoparticles
factorial design
Issue date19-Nov-2019
PublisherMDPI
JournalPolymers
CitationJose, Sajan; Cinu, Thomas A.; Sebastian, Rosmy; Shoja, M. H.; Aleykutty, N. A.; Durazzo, Alessandra; Lucarini, Massimo; Santini, Antonello; Souto, Eliana, Transferrin-conjugated docetaxel-PLGA nanoparticles for tumor targeting: influence on MCF-7 cell cycle. Polymers, 11(11), 1905, 2019
Abstract(s)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.
TypeArticle
DescriptionSupplementary Materials: The following are available online at http://www.mdpi.com/2073-4360/11/11/1905/s1, Figure S1. FTIR spectrum of docetaxel trihydrate (DCT) (upper), of physical mixture of docetaxel trihydrate, transferrin (Tf) and PLGA (middle), and of DCT-loaded Tf-conjugated PLGA NPs (lower); Figure S2. DSC thermogram of PLGA (A), transferrin (B), docetaxel trihydrate (C), their physical mixture (D) and of DCT-loaded Tf-conjugated PLGA NPs (E); Figure S3. (A) X-ray diffraction pattern of docetaxel trihydrate, (B) physical mixture of docetaxel trihydrate, transferrin and PLGA, and of (C) DCT-loaded Tf-conjugated PLGA NPs. Figure S4. (A) Particle size distribution and average particle size and (B) zeta potential of DCT-loaded Tf-conjugated PLGA NPs.
URIhttp://hdl.handle.net/1822/62392
DOI10.3390/polym11111905
e-ISSN2073-4360
Publisher versionhttp://www.mdpi.com/journal/polymers
Peer-Reviewedyes
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series

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