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Molecules 2017, 22(7), 1089; doi:10.3390/molecules22071089

Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery

1
Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
2
Department of Pharmaceutical Sciences, West Coast University School of Pharmacy, 590 Vermont Ave, Los Angeles, CA 90004, USA
*
Author to whom correspondence should be addressed.
Received: 28 April 2017 / Revised: 15 June 2017 / Accepted: 27 June 2017 / Published: 30 June 2017
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
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Abstract

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) (En), poly(l-lysine) (Kn), 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 E51/K55 and E135/K127, however, no complexes were observed when E22 or K21 were used, even in combination with the longer chains. (HE)20/K55 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/K55 PEC dissociated between pH 4.0 and 3.0. These values for pH-dependent particle dissociation are consistent with the pKa’s of the ionizable groups in each formulation and indicate that the specific pH-sensitivity of (HE)20-dauno/K55 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. View Full-Text
Keywords: polyelectrolyte complexes; drug delivery; pH-sensitive; histidine polyelectrolyte complexes; drug delivery; pH-sensitive; histidine
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Folchman-Wagner, Z.; Zaro, J.; Shen, W.-C. Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery. Molecules 2017, 22, 1089.

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