Arginine-[alpha], [beta]-dehydrophenylalanine Dipeptide Nanoparticles for pH-Responsive Drug Delivery

Purpose Nanoparticles (NPs) exhibiting responsiveness towards pH variations in organs, tissue microenvironments and cellular compartments can significantly add on to the drug delivery potential. Here, we have developed NPs from an amphipathic dipeptide, Arginine-[alpha], [beta]-dehydrophenylalanine...

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Bibliographic Details
Published in:Pharmaceutical research 2018-02, Vol.35 (2)
Main Authors: Singh, Pankaj Kumar, Chibh, Sonika, Dube, Taru, Chauhan, Virander Singh, Panda, Jiban Jyoti
Format: Article
Language:English
Subjects:
Analysis
Arginine
Drug delivery systems
Drugs
Hydrogen-ion concentration
Product development
Vehicles
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Summary:Purpose Nanoparticles (NPs) exhibiting responsiveness towards pH variations in organs, tissue microenvironments and cellular compartments can significantly add on to the drug delivery potential. Here, we have developed NPs from an amphipathic dipeptide, Arginine-[alpha], [beta]-dehydrophenylalanine (R[DELTA]F), and tried to explore their pH responsive drug delivery potential in various cancer cells. Methods R[DELTA]F-NPs were architectured by harnessing the process of molecular self-assembly followed by the assessment of effect of pH on NPs morphology using zetasizer, SEM and CD. FTIR and PXRD analysis of the dipeptide and doxorubicin (Dox) were carried out for compatibility assessment followed by encapsulation of Dox in R[DELTA]F-NPs. R[DELTA]F-Dox-NPs were evaluated for pH dependent release as well as for in-vitro cellular internalization and efficacy in cancer cells. Results R[DELTA]F self-assembled to form monodispersed particles at pH 7. SEM analysis revealed a loss of overall particle morphology along with particle aggregation at highly acidic and basic pH respectively. The NPs demonstrated a slow and sustained release behaviour at pH 7 (97.64 ± 4.71% after 36 h) in comparison to pH 2 (90.27 ± 1.45% after 8 h) and pH 10 (96.39 ± 3.87% after 12 h). In-vitro efficacy studies carried-out in various cancer cells revealed that R[DELTA]F-Dox-NPs exhibited higher efficacy with 1.65, 1.95 and 13.34 fold lower IC.sub.50 values in comparison to Dox in C6, HCT-116 and AGS cell lines. Conclusions R[DELTA]F-Dox-NPs with higher drug release at acidic pH, enhanced internalization in cancer cells along with higher cytotoxic potential can act as effective pH responsive drug delivery systems.
ISSN:0724-8741
DOI:10.1007/s11095-017-2299-8