Journal
MOLECULES
Volume 22, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/molecules22071089
Keywords
polyelectrolyte complexes; drug delivery; pH-sensitive; histidine
Funding
- NIH National Cancer Institute [R21 CA169841]
- University of Southern California (USC) Ming Hsieh Institute for Research of Engineering-Medicine for Cancer
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Polyelectrolyte complexes (PECs) are self-assembling nano-sized constructs that offer several advantages over traditional nanoparticle carriers including controllable size, biodegradability, biocompatibility, and lack of toxicity, making them particularly appealing as tools for drug delivery. Here, we discuss potential application of PECs for drug delivery to the slightly acidic tumor microenvironment, a pH in the range of 6.5-7.0. Poly(L-glutamic acid) (E-n), poly(L-lysine) (K-n), and a copolymer composed of histidine-glutamic acid repeats ((HE)(n)) were studied for their ability to form PECs, which were analyzed for size, polydispersity, and pH sensitivity. PECs showed concentration dependent size variation at residue lengths of E-51/K-55 and E-135/K-127, however, no complexes were observed when E-22 or K-21 were used, even in combination with the longer chains. (HE)(20)/K-55 PECs could encapsulate daunomycin, were stable from pH 7.4-6.5, and dissociated completely between pH 6.5-6.0. Conversely, the E51-dauno/K-55 PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the pK(a)'s of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE)(20-dauno)/K-55 PECs is mediated by incorporation of histidine. This response within a pH range that is physiologically relevant to the acidic tumors suggests a potential application of these PECs in pH-dependent drug delivery.
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