Responsive nanogels for application as smart carriers in endocytic pH-triggered drug delivery systems

[Display omitted] •Poly(NIPA-co-AAc) NGs were prepared in different composition of NIPA/AAc.•NG presented excellent dispersability at pH 7.4 and 5 at 37°C.•The NGs were non cito-toxic for models cells.•NGs present high drug loading capacity and efficiency of DOXO·HCl.•A minimal leakage of DOXO·HCl a...

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Bibliographic Details
Published in:European polymer journal 2016-05, Vol.78, p.14-24
Main Authors: Cuggino, Julio César, Molina, Maria, Wedepohl, Stefanie, Igarzabal, Cecilia Inés Alvarez, Calderón, Marcelo, Gugliotta, Luis Marcelino
Format: Article
Language:English
Subjects:
Cancer
Carriers
Carriers, Drug
Doxorubicin
Drug delivery
Drug delivery systems
Drugs
Ionic complexes
Nanogels
Nanomedicine
Nanostructure
NIPA-co-AAc
pH triggered
Therapy
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Summary:[Display omitted] •Poly(NIPA-co-AAc) NGs were prepared in different composition of NIPA/AAc.•NG presented excellent dispersability at pH 7.4 and 5 at 37°C.•The NGs were non cito-toxic for models cells.•NGs present high drug loading capacity and efficiency of DOXO·HCl.•A minimal leakage of DOXO·HCl at pH 7.4 and a triggered release at pH 5 was observed. Various specially designed poly(N-isopropylacrylamide-co-acrylic acid) (NIPA-co-AAc) nanogels (NGs) with different NIPA/AAc molar composition were synthesized by precipitation/dispersion polymerization and evaluated as carriers for drug delivery systems (DDSs) of doxorubicin hydrochloride (DOXO·HCl) for cancer therapies. The NGs presented excellent dispersability in physiological environments (pH 7.4 and 5 at 37°C), as shown by dynamic light scattering (DLS). Moreover, the NGs exhibited high drug loading capacity and efficiency due to the ionic interaction of the cationic drug with the anionic NGs. NG-DOXO·HCl formulation presented excellent dispersability in water and minimal leakage of the cargo at plasma simulated medium (pH 7.4 and 0.14M NaCl) at 37°C and a triggered release at lysosomal simulated medium (pH 5 and 0.14M NaCl). This release behavior together with their size and the low cytotoxicity determined by the MTT assay converts these NGs in great candidates for their application as carriers in cancer therapies based on the enhanced permeability and retention effect (EPR) with drug pH-triggered release after endocytosis in tumor cells.
ISSN:0014-3057
1873-1945
DOI:10.1016/j.eurpolymj.2016.02.022