pH-Responsive Nano Carriers for Doxorubicin Delivery

• Published in: Pharmaceutical research Vol. 32; no. 4; pp. 1249 - 1263
• Main Authors: Bagherifam, Shahla, Skjeldal, Frode Miltzow, Griffiths, Gareth, Mælandsmo, Gunhild M., Engebråten, Olav, Nyström, Bo, Hasirci, Vasif, Hasirci, Nesrin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-04-2015; Springer Nature B.V
• Subjects: Anhydrides - chemistry; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Decanoic Acids - chemistry; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug delivery systems; Drug Liberation; Fourier transforms; Histidine - chemistry; Humans; Hydrogen-Ion Concentration; Macrophages - drug effects; Macrophages - metabolism; Medical Law; Nanocapsules - chemistry; Nanoparticles; Particle Size; Pharmacology; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Research Paper; Surface Properties; polysebacic anhydride; doxorubicin; nanocapsule; poly L-histidine; pH-responsive
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1530-0

Purpose
The aim of this study was to design stimuli-responsive nanocarriers for anti-cancer drug delivery. For this purpose, doxorubicin (DOX)-loaded, polysebacic anhydride (PSA) based nanocapsules (NC) were combined with pH-sensitive poly (L-histidine) (PLH).
Method
PSA nano-carriers were first loaded with DOX and were coated with poly L-histidine to introduce pH sensitivity. The PLH-coated NCs were then covered with polyethylene glycol (PEG) to reduce macrophage uptake. The drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH5) and physiological (pH 7.4) media. The physical and chemical properties of the nanocapsules were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV–VIS), and scanning electron microscopy (SEM).
In vitro
studies of the prepared nanocapsules were conducted in MDA-MB-231 breast cancer cells.
Results
The results obtained by SEM and DLS revealed that nanocapsules have spherical morphology with an average size of 230 nm. Prepared pH sensitive nanocapsules exhibited pH-dependent drug release profile and promising intracellular release of drug. PEGylation of nanoparticles significantly prevented macrophage uptake compared to non-PEGylated particles.