Premium
In vitro characterization of the immunotoxic potential of pH‐sensitive microspheres on macrophage Raw 264.7 (LB639)
Author(s) -
Youan Bi Botti,
Miezan Ezoulin, Miezan,
Zhang Tao
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb639
Subject(s) - reactive oxygen species , chemistry , nitric oxide , zeta potential , glutathione , in vitro , biochemistry , biophysics , biology , nanoparticle , nanotechnology , materials science , organic chemistry , enzyme
The objective of this study is to design pH‐sensitive microspheres (MS) for vagina delivery of microbicides to prevent HIV transmission. The MS were prepared by spray‐drying technique using pH‐sensitive polymethacrylate polymer (S‐100). The MS had a particle size of 76 ̶ 172 nm (in phosphate buffer, pH 7.3) and 6 ̶ 10 µm (in acetate buffer, pH 3.7) along with respective zeta potential in these media of ‐20 and ‐2 mV. It was hypothesized that because of the biocompatibility of the native materials, the MS will be non‐immunotoxic and suitable for the intended application. Methods: cultured murine macrophages RAW 264.7 were exposed for 24h to MS at 1‐1000 μg/mL. Cell membrane integrity, mitochondrial respiration, mitochondrial mass and membrane potential (∆Ψ), reactive oxygen species (ROS), glutathione (GSH) content, and the pro‐inflammatory mediator nitric oxide (NO°) were assessed using standardized in vitro assays. Results: the MS were shown to elicit no cell death at all concentrations tested. The mitochondrial functions were maintained intact except an increase in ∆Ψ (40%) at 1000 μg/mL MS. The MS had no effect on the cellular redox status reflected by the maintenance of ROS and GSH basal levels. Moreover, the MS did not activate the macrophages as evidenced by the basal level of NO°, suggesting an absence of iNOS‐induced inflammation. Conclusions: these findings further support the above working hypothesis, showing the MS as potential nanocarriers for HIV microbicides. Grant Funding Source : RO1A1087304