Designing hybrid onconase nanocarriers for mesothelioma therapy: a Taguchi orthogonal array and multivariate component driven analysis.
Designing hybrid onconase nanocarriers for mesothelioma therapy: a Taguchi orthogonal array and multivariate component driven analysis.
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DOI：
10.1021/mp500403b
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发表时间：
2014-09
影响因子：
4.9
通讯作者：
R. Tekade;Susanne R. Youngren-Ortiz;Haining Yang;Rahul V. Haware;M. Chougule
中科院分区：
文献类型：
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作者：
R. Tekade;Susanne R. Youngren-Ortiz;Haining Yang;Rahul V. Haware;M. Chougule
Onconase（ONC）是核糖核酸酶超家族的成员，其对恶性间皮瘤（MM）具有细胞抑制活性。本研究的目的是开发基于牛血清白蛋白（BSA）-壳聚糖的混合纳米制剂，用于将ONC有效递送至MM，同时最大限度地减少对正常组织的暴露。使用田口正交阵列L9型设计来配制平均粒径为15.78 ± 0.24 nm（λ = -21.89 ± 0.11 mV）的负载ONC的BSA纳米载体（ONC-ANC）。使用范围在0.100和0.175%w/v之间的不同壳聚糖浓度使ONC-ANC表面杂交，以形成各种负载ONC的杂化纳米载体（ONC-HNC）。所获得的数据集进行了分析，通过主成分分析（PCA）和主成分回归（PCR）解码的影响，调查设计变量。主成分分析显示，研究的设计变量，如BSA，乙醇稀释度，总乙醇与粒径和包封率（EE）的配制纳米载体之间的正相关性。PCR结果表明，粒径大小与BSA、乙醇稀释度和总乙醇含量有关，而EE仅受BSA含量的影响。通过PCR对用于ONC-ANC包衣的壳聚糖和TPP效应的进一步分析证实，与未包衣的ONC-ANC相比，它们对粒径、zeta电位和ONC释放的延长具有积极影响。初步稳定性研究的PCR分析显示，在较低pH下，粒径和zeta电位增加。然而，开发的HNC的粒径、zeta电位和EE低于63 nm、31 mV、30 mV和10 mV。和96%，表明它们在所用缓冲液条件下的稳定性。在开发的制剂中，与ONC和ONC-ANC相比，HNC显示出对人MM-REN细胞的细胞活力的抑制增强，IC 50较低。这可能归因于HNC的更好的细胞摄取，这在细胞摄取荧光研究中得到证实。这些研究表明，开发的纳米药物方法可能有助于降低ONC的治疗剂量，通过限制ONC暴露于正常组织来最大限度地减少不良反应，并有助于开发新的治疗形式和给药途径。
Onconase (ONC) is a member of a ribonuclease superfamily that has cytostatic activity against malignant mesothelioma (MM). The objective of this investigation was to develop bovine serum albumin (BSA)-chitosan based hybrid nanoformulations for the efficient delivery of ONC to MM while minimizing the exposure to normal tissues. Taguchi orthogonal array L9 type design was used to formulate ONC loaded BSA nanocarriers (ONC-ANC) with a mean particle size of 15.78 ± 0.24 nm (ζ = -21.89 ± 0.11 mV). The ONC-ANC surface was hybridized using varying chitosan concentrations ranging between 0.100 and 0.175% w/v to form various ONC loaded hybrid nanocarriers (ONC-HNC). The obtained data set was analyzed by principal component analysis (PCA) and principal component regressions (PCR) to decode the effects of investigated design variables. PCA showed positive correlations between investigated design variables like BSA, ethanol dilution, and total ethanol with particle size and entrapment efficiency (EE) of formulated nanocarriers. PCR showed that the particle size depends on BSA, ethanol dilution, and total ethanol content, while EE was only influenced by BSA content. Further analysis of chitosan and TPP effects used for coating of ONC-ANC by PCR confirmed their positive impacts on the particle size, zeta potential, and prolongation of ONC release compared to uncoated ONC-ANC. PCR analysis of preliminary stability studies showed increase in the particle size and zeta potential at lower pH. However, particle size, zeta potential, and EE of developed HNC were below 63 nm, 31 mV, and 96%, respectively, indicating their stability under subjected buffer conditions. Out of the developed formulations, HNC showed enhanced inhibition of cell viability with lower IC50 against human MM-REN cells compared to ONC and ONC-ANC. This might be attributed to the better cell uptake of HNC, which was confirmed in the cell uptake fluorescence studies. These studies indicated that a developed nanotherapeutic approach might aid in reducing the therapeutic dose of ONC, minimizing adverse effects by limiting the exposure of ONC to normal tissues, and help in the development of new therapeutic forms and routes of administration.