Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery.
Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery.
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DOI：
10.3390/molecules22071089
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发表时间：
2017-06-30
期刊：
影响因子：
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通讯作者：
Shen WC
中科院分区：
文献类型：
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作者：
Folchman-Wagner Z;Zaro J;Shen WC
聚电解质复合体(PECs)是一种自组装的纳米结构，与传统的纳米载体相比具有许多优点，包括尺寸可控、生物可降解性、生物相容性和无毒性，这使得它们作为药物输送工具特别有吸引力。在这里，我们讨论了PECS在弱酸性肿瘤微环境中的潜在应用，该微环境的pH范围为6.5-7.0。研究了聚(L-谷氨酸)(EN)、聚(L-赖氨酸)(Kn)和由组氨酸-谷氨酸重复序列((HE)n)组成的共聚物形成PECs的能力，并对其大小、多分散性和pH敏感性进行了分析。在E51/K55和E135/K127的残基长度上，PECS的大小随浓度的变化而变化，而当使用E22或K21时，即使与较长的链结合，也没有观察到复合物。(HE)20/K55PECs能包被柔红霉素，在pH 7.4~6.5范围内稳定，在pH 6.5~6.0范围内完全解离。相反，E51-Dauno/K55 PEC在pH 4.0~3.0之间解离。这些pH依赖的粒子解离的值与每个配方中可电离基团的pKa是一致的，表明(HE)20-dauno/K55 PECS的特定pH敏感性是通过组氨酸的掺入而调节的。在与酸性肿瘤生理相关的pH范围内的这种反应表明，这些PECs在pH依赖的药物输送中有潜在的应用。
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.